Professional Documents
Culture Documents
Quantitative Pharmaoeutical, Ohemistry
Quantitative Pharmaoeutical, Ohemistry
PHARMAOEUTICAL,
OHEMISTRY
CONTAINING THEORY AND PRACTICE OF
QUANTITATIVE ANALYSIS APPLIED
TO PHARMACY
BY
GLENN L. JENKINS, PH.D.
Profes80r of Pharmaceutical Chemi8try, Colle(Jo of Pharmacy,
Uni.eraity of Minnesota
AND
SECOND EDITION
GIPD-S3-,.];)irVRlMa..,.5.7.S7-200:
McGRAW-HILL PUBLICATIONS IN PHARMACY
QUANTITATIVE PHARMACEUTICAL
CHEMISTRY
McGRAW-HILL PUBLICATIONS IN
PHARMACY
A SERIES OF TEXTS AND REFFERENCE WORKS
OUTLINED BY THE FOLLOWING COMMITTEE
C. W. JOHNSON, Chairman,
Dean, University of Washington, College of Pharmacy.
EDWARD SPEASE, Acting Chairman and Consulting Ed7.'tOT,
Dean, Western Reserve University, School of Pharmaoy.
JOHN G. BEARD,
Professor of Pharmacy, University of North Carolina,
School of Pharmacy.
W. W. OHARTERS,
Direqtor of the Bureau of Educational Research, Ohio
State University. Recently Director in Charge of the
Commonwealth Study of Pharmacy.
H. C. CHRISTENSEN,
Secretary National Assooiated Boards of Pharmacy,
Chicago, Illinois.
ZADA M. COOPER,
Associate Professor of Pharmaoy, State University of
Iowa, College of Pharmacy.
ANDREW G. DuMEZ,
Dean, University of Maryland, School of Pharmaoy.
CLAIR A. DYE,
D'l"n, Ohio State University, College of Pharmaoy.
D. B. R. JOHNSON,
Dean, University of Oklahoma, Sohool of Pharmacy.
C. B. JORDAN,
Dean, Purdue Uiiiver~ity, School of Pharmacy.
TOWNES R. LEIGH,
Dean, University of Florida, School of Pharmacy.
RUFus A. LYMAN.
Dean. University of Nebraska, College of Pharmaoy.
WORTLEY F. RUDD,
Dean, Medical College of Virginia. Sohool of Pharmaoy.
CHAS. H. STOCKING,
Associate Professor of Pharmaoy, University of Michi-
gan, College of Pharmaoy.
ARNO VIEHOEVER t
Profeasor of Biology and Pharmacognosy, Philadelphia
College of Pharmacy.
A. L.I. WINNE,
Secretary, Virginia State Board of Pharmacy, Richmond.
Virginia.
McGRAW -HILL
PUBLICATIONS IN PHARMACY
The wide popularity that the first edition of thi~ book has
enjoyed among students and teachers has been gratifying to the
publishers and to the authors. It is hoped that the new edition
will similarly commend itself to a still larger circle. To the many
kind friends who have so generously aided by means of helpful
suggestions, the authors desire to express their thanks.
GLENN L. JENKINS.
ANDREW G. DuMEZ.
MINNEAPOLIS, MINN.
BALTIMORE, MD.,
February, 1937.
PREFACE TO THE FIRST EDITION
The object of this book is twofold: First, to furnish students of
pharmacy with a systematic course covering all of the quantita-
tive chemical and physical methods official in the United States
Pharmacopoeia and the National Formulary through the selec-
tion and explanation of typical procedures. Second, to present
some of the generally applicable, non-official methods of analysis
which are widely used in pharmacy and with which all students
pursuing the profession should be familiar. In 'both instances,
the theory and practice of analytical chemistry as applied in
quantitative pharmaceutical procedures have been correlated.
The use of the book as a text should be supplemented by lec-
ture and recitation instruction. It is obviously impracticable to
include detailed explanations of all of the quantitative determi-
nations in the Pharmacopoeia and National Formulary. Typical
analyses illustrating all of the various methods have therefore
been selected and explained in considerable detail, while those
determinations requiring the same or closely similar procedures
are indicated in tables or otherwise. The instructor may select
other determinations from the Pharmacopoeia or National
Formulary and assign to the students the task of applying the
theory and explanation of the procedure involved as given in the
text.
The book is divided into four parts. Part I is intended for
use with students who have ~ompleted a full year of work in
general inorganic chemistry and qualitative analysis. Parts
II and III preferably should be given after the students have
eompleted inorganic and organic chemistry. Part IV should be
given to advanced students who have acquired a thorough knowl-
edge of quantitative technique. In the authors' classes, Part I
is given during the second half of the second year in a course
covering sixteen weeks with one four-hour laboratory period
each week. In this course/ about twenty assays a.re performed
ix
x PREFACE TO THE FIRST EDITION
INTRODUCTION . . . . . . . . xix
Definitions and scope of quantitative pharmaceutical chemistry-
References.
PART I
General Methods Used in Official Pharmaceutical Analyses
CHAPTER I
REMARKS AND GENERAL DIRECTIONS . . . . 3
Sampling-Calculation of results and errors-General operations-
The analytical balance-Weights.
CHAPTER II
GRAVIMETRIC ANALYSIS . . . . . . . 29
Theory of ionization-Reversible reactions-Solubility product
principle-Common ion effect.
CHAPTER III
GRAVIMETRIC METHODS . . 37
Assay of sodium chloride, of sodium sulfate, of mercuric chloride, of
calcium glycerophosphate, of alum, and of solution of magnesium
citrate.
CHAPTER IV
PRINCIPLES OF VOLUMETRIC (TITRIM,ETRIC) ANALYSIS. 57
Definitions-Volumetric apparatus-The calibration of volumetric
apparatus-Neutralization .. method~: Theory-Indicators-
Standard solutions-Preparation and standardization of normal
hydrochloric acid, of normal sodium hydroxide, and of tenth-
normal barium hydroxide.
CHAPTER V
ALKALIMETRY . . . . . . . 86
Direct titration methods: Assay of sodium bicarbonate, of sodium
hydroxide, and of sodium salicylate.
xi
xu CONTENTS
PAGE
Residual titration methQds: Assay of zinc oxide, of potassium and
sodium tartrate, of magnesia magma, of methenamine; of solu-
tion of ammonium acetate, and estimation of nitrogen by' the
Kjeldahl method.
CHAPTER VI
ACIDIMETRY . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Direct titration methods: Assay of diluted sulfuric acid, of boric
acid, of tablets of sodium salicylate, and of tartaric acid.
Residual titration methods: Assay of aromatic sulfuric acid ~ntf of
tablets of acetylsalicylic acid.
CHAPTER VII
PRECIPITATION METHODS . . . . . . . . . . . . . . . . . . . . 116
Determination of the end point-Indicators. Standard solktions.
Preparation and standardization of tenth-normal silver nitrate and
of tenth-normal ammonium thiocyanate.
Direct titration methods: Assay of strong silver protein.
Residual titration methods: Assay of sodium chloride, of ammo-
nium bromide, of syrup of hydriodic acid, and of elixir of three
bromides.
CHAPTER V~II
OXIDATION-REDUCTION METHODS • . • . . . . . . . . . . . .,129
. .
Theory-Standard solutions-Preparation and stanaardization of
tenth-normal p'otassium permanganate.
Direct titration methods: Assay of ferrous sulfate, of reduced
iron, and of solution of hydrogen peroxide.
Indirect titration methods: Assay of calcium gluconate.
Residual titration methods: Preparation and standardization of
tenth-normal oxalic acid-Assay of sodium nitrite, of pre~
cipitated calcium carbonate, and of potassium chlorate.
Dichromate methods: Preparation of tenth-normal potassium
dichromate-Assay of mass of ferrous carbonate.
CHAPTER IX
OXIDATION AND REDUCTION-IoDOMETRIC METHODS . . . . . . . . . 155
Starch indicator solutions. Standard solutions: Preparation and
standardization of tenth-normal sodium thiosulfate solution
and of tenth-normal iodine.
Direct titration with standard iodine solution: Assay of arsenic
trioxide.
Direct titration with sodium thiosulfate: Assay of compound
solution of iodine.
Residual titration with standard sodium thiosulfate: Assay of
mercurous chloride.
CONTENTS xiii
PAGE
Titration of the iodine liberated from potassium iodide with sodium
thiosulfate: Assay of solution of ferric chloride, of chlorinated
lime, qf cupric sulfate, of sodium arsenate, of thyroid, and of
spirit of ethyl nitrite.
Titration with tenth-normal bromine: Preparation and standardi-
zation of tenth-normal bromine--Assay of phenol and of
ammonium hypophosphite.
Titrations with standard potassium iodate: Preparation of standard
potassium iodate solution-Assay of potassium iodide.
CHAPTER X
GASOMETRIC METHODS . . . . . . . . . . . . . . . . 188
Theory...--Apparatus-Test of the nitrometer-Assay of carbon
dioxide and of spirit of ethyl nitrite.
PART II
Pl5.ysical Methods Used in Official Pharmaceutical Analyses
CHAPTER XI
SOLUBI}!iITY. . . . . . . . . . . . . . . . . . . . . . . . . . . 203
l)efinitions.
Determination of the solubility of boric acid in water at 25°C.
CHAPTER XII
SPECIFIC GRAVITY AND DENSITY . . . . . . . . . . . . . . . .. 207
Methods used to determine the specific gravity of liquids: The use
of pycnometers-Determination of the alcohol content of an
official preparation. The use of the Westphal balance-Deter-
mination of the specific gravity of a volatile oil. The use of
hydrometers.
Methods used to determin~ the specific gravity of solids: B~ weigh-
ing in water-Determination of the specific gravity of camphor:
By the flotation method-Determination of the specific gravity
of yellow wax.
CHAPTER XIII
MELTING, CONGEALING, AND BOILING POINTS. . . . . . . . . . . . 226
Melting point: Determination of the melting point of salicylic acid.
Congealing point: Method of determining-Determination of the
solidification temperature of the fatty acids of cottonseed oil.
Boiling and distilling point: Determination of the boiling point of
carbon tetrachloride.
xiv CONTENTS
PAGE
CHAPTER XIV
REFRACTOMETRIC MEASUREMENTS . . . . . . . 240
Refractive index: Refractometers-The Abbe refractometer.
Determination of the refractive index of oil of oran~e.
CHAPTER XV
ROTATORY POWER . . . . 247
Definitions-Polarimeters.
Determination of the specific rotation of sucrose.
CHAPTER XVI
VISCOSITY MEASUREMENTS. . 257
Definitions-Apparatus: The Saybolt viscosimeter.
Determination of the kinematic viscosity of liquid petrolattlm.
CHAPTER XVII
PHOTOMETRIC METHODS OF ANALYSIS. . . . . . . . . . . . . . • 260
Colorimetry: Determination of the ammonia contellt of water-
Determination of the amount of epinephrine hyclrochlori1.e in
solution of epinephrine hydrochloride-Assay of crPCUS for color.
Nephelometry: Determination of the amount of arsep-ic trioxide in
solution of arsenous acid-Determination of the aJjlount of oil of
peppermint in spirit of peppermint and limit test for chloride an.d
sulfate in calcium gluconate.
CHAPTER XVIII
DETERMINATION OF HYDROGEN ION CONCENTRATION ...... 272
Acid base equilibrium and pH.
Potentiometric methods: The hydrogen electrode-rPlatinization
of the hydrogen electrode-The calomel electrode--The scheme
of assembly for hydrogen ion methods.
Determination of the end point of titration of hydrochloric acid
with sodium hydroxide potentiometrically-Notes and pre-
cautions-Determination of the end point of titro-tion of acetic
acid with sodium hydroxide potentiometrically. :J)etermination
of the pH of saturated boric acid solution, and or physiological
salt solution.
The quinhydrone electrode: Preparation-Use of.
Determination of the pH of elixir of iron, quinine aJld strychnine,
elixir of pepsin, and tincture of aconite by mean!! of the quin-
hydrone electrode.
The glass electrode.
Colorimetric methods: Indicators-Buffer solutions_,-Color stand-
ards-Color comparators.
Determination of the pH of solution of epinephrine P.ydrochloride,
and syrup of hydriodic acid.
CONTENTS xv
CHAPTER XIX
ELECTROLYTIC ~ETHODS . . . . . . . . . . . . . . . . . . . . . 305
Electrical units and fundamentallaws-Theory-Apparatus.
Assay of copper sulfate and of mercuric chloride. Other electroly-
tic assays.
PART III
Special Methods Use~ in Official Pharmaceutical Analyses
CHAPTER XX
ASH AND ~OISTURE DETERMINATIONS . . . . . . . . . . . . . . . 323
Ash content: Determination of the total and acid-insoluble ash
content of digitalis leaf.
~oisture content: Determination of the moisture content of acacia
-Determination of the moisture content of digitalis leaf by the
toluene distillation method.
CHAPTER XXI
ExTRACTIVE AND CRUDE FillER CONTENT . . . . . . . . . . . . . 336
•
Volatile and non-volatile ether-soluble extractive: Determination
of the volatile and non-volatile ether-soluble extractive of clove.
Alcohol-soluble extractive: Assay of benzoin.
Water-soluble extractive: Assay of aloe.
Purified petroleum benzin extractive.
Crude fiber: Determination of the crude fiber content of cloves.
CHAPTER XXII
CONSTANTS OF FATS, FATTY OILS, WAXES, BALSAMS, RESINS, ETC. . . 345
Acid number: Determination of the acid value of rosin.
Saponification value: Determination of the saponification value of
cottonseed oil.
Ester number.
Unsaponifiable matter.
Iodine value: Determination of the iodine value of olive oil.
CHAPTER XXIII
ASSAY OF VOLATILE OILS . . . . . . . . . . 361
~ethods of general application: Specific gravity-Rotatory power
-Refractive index-Congealing point-Distilling point-Frac-
tional distillation-Solubility.
Assay for ester content: Preparation of half-normal alcoholic potas-
sium hydroxide-Assay of oil of peppermint for total esters.
Assay for alcohol content: Assay of oil of peppermint for total
menthol.
Assay for aldehyde content: Assay of oil of bitter almond for
benzaldehyde content.
xvi CONTENTS
PAGE
Assay for ketone content: Assay of oil of caraway.
Assay for phenol content: Assay of oil of clove.
Assay for hydrocyanic acid content: Assay of oil of bitter almond
for hydrocyanic acid.
Assay 101: ascaridol content: Assay 01 oil of chenopodium.
Assay for allyl isothiocyanate: Assay of oil of mustard.
Assay for volatile oil in spirits: Assay of spirit of peppermint.
CHAPTER XXIV
ALKALOIDAL ASSAYING . . . . . . . . . . . . 386
General principles: Sources of error-Theory of distribution
coefficient-Choice of indicators-Test solutions.
General procedures: Selection of the sample-Extraction with
immiscible solvents-Evaporation of organic solvents-Gravi-
metric determination of alkaloids-Volumetric determina'tion of
alkaloids.
CHAPTER XXV
OFFICIAL TYPE METHODS . . . . . . . . . . . . . . . . . . . . 403
Alkaloidal assays by aliquot-part method.
General procedure: Extraction of the drug-Decanting the aliquot
portion-Shaking out with acid-Shaking out...with immiscible
solvent-Determination of the alkaloidal content.
Gravimetric assays: Assay of hydrastis for ether-solu\>le alka-
loids, of cinchona for total alkaloids, and of compou.nd tincture of
cinchona.
Volumetric assays: Assay of ipecac for ether-soluble alkaloids and
assay of areca.
Alkaloidal assays by the total extraction method: Assay of hyo-
scyamus leaves.
Assay of preparations of hyoscyamus, belladonna, and stramonium:
Assay of tincture of belladonna and fluidextract of belladonna
leaf.
CHAPTER XXVI
ALKALOIDAL ASSAYS BY SPECIAL METHODS . . . 418
Assay of opium.
Table of official substances assayed by the same met.hod as opium.
Assay of colchicum.
Table of substances assayed by the same method as colchicum.
Assay of nux vomica.
Assay of caffeine containing drugs:-Assay of guaranlt.
Table of official drugs and preparations assayed for caffeine.
Assay of alkaloidal salts: Assay of citrated caffeille, of eucaine
hydrochloride, of theobromine with sodium salicylate, and of
theophylline with sodium acetate.
CONTENTS ~vii
PAGE
CHA'pTER XXVII
OTHER OFFICIAL ASSAYS INVOLVING THE USE OF IMMISCIBLE SOLVENTS 437
Assay of cantharides-Assay of aspidium-Assay of jalap-Assay
of tablets of phenobarbital.
CHAPTER XXVIII
ASSAY OF ENZYME-CONTAINING SUBSTANCES . . . . . . . . . . . . 444
Assay of pepsin-Assay of pancreatin for starch digestive power-
Assay of pancreatin for casein digestive power-Asflay of rennin.
INDEX . . . . . . 457
Textbooks
1. BASSET, "The Theory of Quantitative Analysis," Alfred A. Knopf, Inc.,'
New York, 1925.
2. BLASDALE, "Principles of Quantitative Analysis," 3d ed., D. Van
Nostrand Company, Inc., New York, 1928.
3. CLOWES and COLEMAN, "Quantitative Chemical Analysis," 13th ed.,
P. Blakiston's Son & Company, Philadelphia, 1931.
4. CUMMINS and KAY, "A Textbook of Quantitative Chemical Analysis,"
6th ed., Gurney and Jackson, London, 1934.
5. ENGELDER, "Elementary Quantitative Analysis," 2d ed., John Wiley
& Sons, Inc., New York, 1936.
INTRODUCTION XXI
Calculations
1. HAMILTON and SIMPSON, "Calculations of Quantitative Analysis,"
2d ed., McGraw-Hill Book Company, Inc., New York, 1927.
2. LONG and ANDERSON, "Chemical Calculations," 3d I'd., McGraw-Hill
Book Company, Inc., New York, 1936.
3. MELLOR, "Higher Mathematics for Students of Chemistry and
Physics," 4th I'd., Longmans, Green & Company, New York, 1922.
4. MILLER, "Calculations of Analytical Chemistry," 3d I'd., McGraw-
Hill Book Company, Inc., 1921.
5. MOORE, "Logarithmic Reduction Tables, for Students of AnaJytical
Chemistry," Ginn and Company, Boston, 1913.
xxii INTRODUCTION
General References
l. ALLEN, "Commercial Organic Analysis," 5th ed., P. Blakiston's Son &
Company, Philadelphia, 1926.
2. GOOCH, "Methods in Chemical Analysis," John Wiley & Sons, Inc.,
New York, 1912.
3. GRIFFIN, "Technical Methods of Analysis," McGraw-Hill Book Com-
pany, Inc., New York, 1921.
4. KOLTHOFF and FURMAN, "Volumetric Analysis," JollD Wiley & Sons,
Inc., New York, 1929.
5. MELLOR, "A Treatise on Quantitative Inorganic Analysis," Charles
Griffin & Company, Ltd., London, 1913.
6. SCOTT, "Standard Methods of Chemical Analysis," 4th ed., D. Van
Nostrand Company, Inc., New York, 1925.
7. SMITH, "Analytical Processes," Edward Arnold and do., London, 1929.
8. SUTTON, "Volumetric Analysis," 12th ed., P. Blakiston's Son & Com-
pany, Philadelphia, 1935.
9. TRE.A.DWE.L.L. and HA.LL., "Q.uantitative A.n.al,!si"':' stU ed ... John Wiley
& Sons, Inc., New York, 1935.
10. VILLAVECCHIA, "Applied Analytical Chemistry," p.J3lakiston's Son &
Company, Philadelphia, 1918.
Drug Analysis
1. DRAGENDORFF, "Plant Analysis, Qualitative and Quantitative,"
Balliere, Tindall and Cox, London, 1884.
2. EVERS and ELSDON, "Analysis of Drugs and Chemicals," Charles
Griffin and Company, London, 1929.
3. FULLER, "The Chemistry and Analysis of Drugs and Medicines," John
Wiley & Sons, Inc., New York, 1920.
4. LYONS, "Practical Standardization of Drugs," Nelson & Co., Detroit,
1920.
5. "National Formulary VI," 6th ed., Mack Printing Oompany, Easton,
Pa., 1936.
6. NELSON, "Introduction to the Analysis of Drugs and Medicines," John
Wiley & Sons, Inc., New York, 1910.
7. "New and Non-official Remedies" ("N.N.R."), MDerican Medical
Association, Chicago, 1936.
8. "Pharmacopoeia of the United States XI," 11th rev., Mack Printing
Company, Easton, Pa., 1936.
Food Analysis
1. BLYTH, "Foods, Their Composition and Analysis" 6th ed., D. Van
Nostrand Company, Inc., New York, 1909.
INTRODUCTION xxiii
SAMPLING
ing to methods I, II, and III, the official sample may consist of
the total amount of a direct purchase made by Federal, State or
Municipal Food and Drugs' Act enforcement officials."
Students' samples are supplied ready for analysis as a rule.
Samples which require drying should be spread on a large watch
glass, thoroughly mixed, and dried in an oven at the specified
REMARKS AND GENERAL DIRECTIONS 9
M"gnitude of error +X
FIG. 2.-Probability curve.
24.46 X 0.2917
1000 X 0.003741
10.8613 - 10
10.5730 - 10
0.2883
GENERAL OPERATIONS
Crucibles.-A variety of crucibles are used in quantitative
analysis. Those most commonly employed are made of high-
grade porcelain. They withstand high
temperatures and are suitftble for use
in the ignition of most '.p.rugs and
precipitates. They are not suitable
for fusions because the glaze is attacked
by the flux, especially if the flux is
basic. Other crucibles consist of fused
silica, alundum, nickel, and p~atinum.
The Gooch Filtration Crucible.-The
Gooch filtration crucible (Fig. 3) is
designed for the separation1of precipi-
tates by suction filtration. It has a
perforated bottom upon which is
bedded a mat of asbestos, thus mak-
FIG. a.-Diagram of Gooch ing it possible to collect, wash, dry,
crucible assembly for filtra- d . h . . .
tion. an weIg a preCIpItate III the saple
crucible.
Preparation and Use of Gooch Crucible.-Obtain about 0.5
Gm. of asbestos fiber (washed with hydrochloric acid) and shake
it thoroughly with 100 cc. of distilled water in a suitable flask.
Allow the asbestos to settle and decant most of the water con-
taining the fine fibers. Add about 100 cc. of water and agitate
the mixture ~gain. Fit the Gooch funnel containing the crucible
in the mouth of a filter flask connected to a suction pump. Pour
the suspended asbestos mixture into the crucible in small succes-
sive portions applying suction gently after the addition of each
portion until a smooth mat not over 1.5 mm. thick is obtained.
Upon holding the crucible to a strong light, the holes in the
REMARKS AND .GENERAL DIRECTIONS 17
RIDER HOOK--__
____INPlCATOR
(OR. NEEDLZl
BowWIRES-
~ __ --.LEV)!:L
PAN---__
.---PAN ARREST
---INPEX PLATE
are then carefully lowered, and if the beam does not swing, it
may be set in motion by means of the rider. Long swings of the
pointer are not necessary. The pointer should swing through an
amplitude of not less than two divisions to either side of the zero
of the index scale.
11. All weights should be handled with the forceps; they should
never be touched with the fingers. Place heavy weights in the
center of the pan to prevent oscillation.
12. Record all weights directly into your notebook upon com-
pletion of a weighing. Before removing weights, check the
balance by arresting and releasing the beam and be sure that
correct balance has been attained. Remember that a slight error
in weighing may render worthless all further analysis of a sample.
13. Before leaving the balance, stop the motion of the beam
by means of the pan arrests, raise the beam off the agate knife.
edges, be sure the balance is clean, and close the door of the
balance case.
Sensitivity of the Analytical Balance.-The sensitivity varies
inversely with the weight of the beam. The lighter the beam,
therefore, the greater the sensitivity. The sensitivity varies
with the length of the beam. The sensitivity varies directly to
the time period of oscillation. The sensitivity varies inversely
with the load on the pans. The sensitivity of a balance may be
varied by moving the small gravity weight on the pointer upward
or downward, thus changing the position of the center of gravity
of the beam. The efficient'operation and sensitivity of a balance
are dependent upon minimum friction between the agate
knife edges and bearings.
Exercise 1
Left Right
5.2 4.6
5.1 4.4
5.0
--
3)15.3 2)9.0
5.1 4.5 average
5 . 1 - 4. 5 = o. 6 difference
0.6/2 = 0.3 of a scale division to the left which is the true zero
point. Make at least three such zero point determinations. The
results should check within two-tenths of a scale division.
The true zero point of a balance varies from day to day and
should be determined each time the balance is used.
Exercise 2
Object.-Determination of the Sensitivity of a Balance.
The difference between the two rest points gives the sensitivity
of the balance in terms of index scale divisions. Assume that the
difference in the rest points is two, then 1 mg. causes a displace-
ment of two scale divisions. Since the index scale can be read
to one-tenth of a division and there are 20 one-tenth divisions,
the balance is said to be sensitive to 0.05 mg.; that is, the smallest
weight which can cause a readable deflection is 0.05 mg.
Determine the sensitivity of the balance with loads of 10 Gm.
on each pan and with 20 Gm. on each pan. Tabulate your
results.
WEIGHTS
Figure 8 illustrates a set of analytical weights. Analytical
weights may be purchased in graduated sets; a set in which the
26 QUANTITATIVE PHARMACEUTICAL CHEMISTRY~
I
Weight, Correction, Correction,
Weight
grams 0.1 mg. 0.1 mg.
I
0.005 0 1.0 +17
0.010 +2 1.0 + 1
O.OlO +3 1.0 +11
0.020 + 3 2.0 + 4
0.050 0 5.0 +32
0.100 + 1 10.0 0
0.100 0 10.0 +12
0.200 +9 20.0 -12
0.500 +10 50.0 +42
GRAVIMETRIC ANALYSIS
THEORY
The student should be familiar with the modern chemical
theories which apply in quantitative analysis from the study of
general chemistry and qualitative analysis. In quantitative
analysis, theoretical considerations must be understood and
applied in order to know the full explanation of what takes place
in an analysis. A brief review of the fundamentals of the various
theories with their quantitative application will be given in
conjunction with those procedures to which they apply.
The reactions of quantitative analysis take place in accordance
with the established laws and theories of chemistry, i.e., theory
of ionization, law of mass action, common ion effect, reversible
reactions, and solubility product principle.
Theory of Ionization.-The theory of ionization is based on
the following postulates:
1. Electrolytes in solution form ions. When electrolytes are
dissolved in water, their molecules dissociate or break up into
particles termed ions; thus, when hydrogen chloride gas is dis-
solved in water, some of the hydrogen chloride molecules disso-
ciate or ionize to form hydrogen ions and chloride ions so that
from one molecule of hydrogen chloride, two ions are obtained.
2. Some of the ions are charged positively, others negatively;
the sum of positive and negative charges always being equal, the
solution remains electrically neutral. In the case of hydrogen
chloride, the hydrogen ions are charged positively and the
chloride ions negatively, the sum of positively charged hydrogen
ions being equal to the sum of negatively charged chloride ions;
the solution of hydrogen chloride gas remains electrically neutral.
3. The properties of the ions into which the electrolyte dis-
sociates differ from the original substance. The hydrogen and
chloride ions have properties different from the original hydrogen
29
30 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
chloride gas, and the hydrogen and chloride ions differ from
hydrogen and chlorine gas, respectively.
4. The ionization of the electrolyte results in an equilibrium.
The point at which equilibrium is reached is dependent on the
nature of the electrolyte, the nature of the solvent, and upon
the dilution; thus, electrolytes differ in the extent to which they
ionize; some solvents, such as ether and benzene, produce no
ionization, but in solvents which produce ionization, the greater
the dilution the greater the extent of ionization of the electrolyte.
A certain state of equilibrium exists between the ions and
undissociated molecules for every degree of dilution. The
equilibrium'''may be represented as follows: NaCI Na+ + Cl-
when sodium chloride is dissolved in water. Since the extent
of dissociation is dependent on dilution, the greater the dilution
of the solution the more sodium chloride will dissociate into ions
until at infinite dilution it may be regarded as completely ionized.
The eqUlI 'l'b . . db h . [Na+J X [Cl-J
num IS represente y t e equatIon [NaCl] =
K where [Na+], [Cl-], and [NaCl] represent the concentration
of sodium ion, chloride ion, and sodium chloride, respectively,
and K represents the ionization constant.
Reversible Reactions.-Most of the reactions iAvolved in
quantitative analysis are of the reversible type. Under certain
conditions they may be made to continue to completion, but
under other conditions they may attain equilibrium before
completion, resulting in loss of a portion of the substance being
analyzed. It, therefore, is very important to understand what
conditions must be satisfied to make the reaction go forward
to completion so that it will be of value in quantitative work.
Thete are three general conditions which tend to destroy equilib-
rium and lead to complete reaction: (1) the formation of an
insoluble gas; (2) the formation of a sparingly soluble solid;
(3) the formation of very slightly ionized molecules.
According to the law of mass action, the speed of a reaction is
proportional to the products of the molecular concentrations of
the teacting substances. Since the speed of a reaction depends
upon the concentration of every substance taking part in the
reaction, the point of equilibrium will depend upon the concen-
tration of each of the components of the two opposing reactionsj
GRAVIMETRIC ANALYSIS 31
+
e.g., in the reaction KNO a H 2S0 4 KHS0 4 +
HNO a, the
speed of the reaction of potassium nitrate with sulfuric acid is
expressed by the equation: _
Speed = (KNO a] X (H 2S0 4] X k where k is the affinity con-
stant of the reaction.
The speed of the opposing reaction is expressed by the equation:
Speed = [KHS0 4 ] X [HNOa] X kl where kl is the affinity con-
stant of the opposing reaction. At equilibrium the speeds of
the two reactions are equal.
and
Temperature, Solubility
Substance Ions involved
°C. product
AgI forms 1 Ag+ ion and 1 I- ion, and the solubility product is
equal to the ionic product
Ou+ X Ox- = 10-8 X 10-8 = 10-16 = S.P. of AgI
From the above calculation of solubility product, it can be
predicted that silver iodide will precipitate if Cu+ X 0 1- becomes
greater than 10- 16 ; that in a supersaturated solution Cu + X Ox-
becomes greater than 10- 16 ; that in a saturated solution OAa+
X Ox- wilJ..be equal to 10-16 ; an(that to dissolve precipitated
AgI, OAa+ X 0 1- must be less than)O-16.
In the above illustration, the solubility product of silver iodide
was calculated from solubility data. Conversely, if the solubility
produce is known, the solubility of a compound may be calcu-
lated. In the table, the solubility product of silver chloride is
given as 1.5 X 10- 10 at 25°C. How much silver chloride will
dissolve in 100 cc. of water at the above temperature?
S,P' AgCI = GAg+ X GCI- = 1.5 X 10- 10
If OAg+ = x, then OCl- = x, since OAg+ = OCl-
x 2 = 1.5 X 10-10
X = 1.22 X 10-5
GRAVIMETRIC METHODS
Gravimetric analysis implies that the substance to be deter-
mined is to be separated from a weighed sample in the form of a
compound of known composition and weighed. Knowing the
weight of the original sample and that of the product, the weight
and percentage of any component common to both can be cal-
culated. The product to be weighed in pharmaceutical analysis
may be obtained by any'one of various methods: (1) It may be
precipitated from solution; (2) it may be the decomposition
product resulting from ignition of a compound; (3) it may be
deposited on an electrode by electrolysis; (4) it may be separated
from other substances by extraction with a solvent; and (5) it
may be obtained by absorbing a gas in some substance of known
weight and finding the increase in weight produced by the absorp-
tion of the gas. The first two methods comprise the subject
matter considered in this chapter.
Exercise 4
Determination of Chloride Ion in a Soluble Chloride.-Chloride
ion is determined gravimetrically by precipitating and weighing it
as silver chloride. An excess of solution of silver nitrate, slightly
acidified with nitric acid, is added to the solution of soluble chlo-
ride. The precipitate is filtered out, washed, dried, and weighed
as silver chloride. Other substances which yield insoluble silver
salts must be absent.
No method for the gravimetric determination of chloride ion is
official, but the procedure constit.utes a classic example of gravi-
metric analytical technique with which every student should be
familiar.
Object.-Assay of Sodium Chloride.
Materials Required.-O.25 Gm. of sodium chloride.
5 per cent silver nitrate solution.
37
38 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Weight of 1 II
Exercise 5
Determination of Sulfate Ion in a Soluble Sulfate.-The
sulfate ion in a soluble sulfate may be determined gravimetrically
GRA VIMETRIC METHODS 43
by precipitation as barium sulfate, the precipitate being collected,
dried, ignited, and wflighed.
Object.-Assay of Sodium Sulfate.
Materials Required.-l Gm. of sodium sulfate.
Barium chloride T.S. (12 per cent).
Procedure.-Weigh accurately about 0.4 Gm. of the dried salt, obtained
by drying about 1 Gm. to constant weight at 120°0., dissolve it in 200 cc.
of distilled water, and add 1 cc. of hydrochloric acid. Heat to boiling, and
gradually add an excess of hot barium chloride T.S. Heat the mixture for
30 min. on a water bath, collect the precipitate of barium sulfate on a filter,
wash it until free from chloride, dry, ignite, and weigh. The weight of the
barium sulfate thus obtained, multiplied by 0.6086, indicates its equivalent
of Na.S04. .
The solution of the sulfate is acidulated with hydrochloric
acid to prevent the precipitation of carbonates, etc., which are
soluble in hydrochloric acid solution. The acid also increases
the solubility of barium sulfate slightly and therefore promotes
the growth of large crystals, since small crystals dissolve more
rapidly than large ones. The small crystals expose more surface
area per unit of weight than do large ones. Consequently, they
dissolve more rapidly, and in a saturated solution the larger
crystals with small surface area exposed grow more rapidly than
they dissolve. The solution is heated to boiling to expel dis-
solved CO 2 • An excess of hot barium chloride solution is added
to insure complete precipitation and to decrease the solubility
of barium sulfate by common ion effect. The mixture is digested
on a water bath for 30 min. to allow the larger crystals to grow
at the expense of the smaller ones, since the latter are more
rapidly soluble.
The barium sulfate is directed to be washed on a filter to
remove excess BaCh and the NaCl formed, but 'the washing
process may be carried out more rapidly by washing once by
decantation. The precipitate is then transferred quantitatively
onto an ashless filter by the same technique used in Exercise 4
and washed free of chlorides vas shown by tests made with silver
nitrate solution on 2 cc. portions of the filtrate. Always acidu-
late the filtrate with a drop of nitric acid in carrying out the test
for chlorides. Sometimes fine-grained crystalline precipitates
will pass through the filter. This may be observed by imparting
a rotatory motion to the filtrate, causing any crystals which
44 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Weight
of Ignition
Substance Factor Official requirement, per cent
sample, residue
Gm.
---
U.S.P.
Lead 8ubaceta teo R .......... 1.0 PbSO. ....... Pb = 70 to 73
Sodium sulfate .............. 0.4 BaSO. 0.6086 Na.SO. = 99
Sulfur ointment ..... ........ 0.5 BaSO. 0.1373 S = 13.5 to 16.5
Sulfur (all forms) ........... 1.0 BaSO. 0.1373 S = 99.5
N.F.
Ichthammol for (NH.),SO •... 1.0 BaSO. 0.5661 (NH.),SO. = not more than 8
Ichthammol for total sulfur ... 1.5 BaSO. 0.1373 S = 10
Potassium guaiacol sulfonate. 1.0 BaSO. 1.03757 C.H 3.OH.OCH 3SO.K = 97
Potassium sulfate ........ , .. 0.6 BnSO. 0.7465 K,SO. = 99
Sodium sulfate exsiccated ... . 0.5 BaSO. 0.6086 Na,SO. - 99
R. = reagent.
Exercise 6
Determination of the Mercury Content of a Mercuric Salt.-
The mercury is precipitated as sulfide, washed, dried, and
weighed.
Object.-Assay of Mercuric Chloride.
Materials Required.-O.5 Gm. of mercuric chloride.
1 cc. of hydrochloric acid.
About 70 cc. of alcohol.
About 40 cc. of carbon tetrachloride.
Procedure.-l. "Dry about 0.5 Gm. of Mercury Bichloride to constant
weight over sulfuric acid, weigh accurately, and dissolve in 300 cc. of warm
distilled water to which 1 cc. of hydrochloric acid has been added. Pass
hydrogen sulfide through the cold solution until the precipitate of ~ercuric
sulfide readily subsides, leaving a clear, supernatant liquid."
46 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Sample,
Resi- Fac- Official requirement,
Substance Gm. or
due tor per cent
cc.
----
U.S.P.
Bismuth and potas-
sium tartrate ..... 0.4 Bi 2S3 0.9063 Bh03 = 71 to 75
Merbaphen ......... 0.5 HgS 0.8622 Hg = 33 to 34.5
Mercuric chloride,
poison tablets of,
large .......... , . 10· HgS 1.167 HgCl2 = 0.45 to 0.55 b
Mercuric chloride,
poison tablets of,
small ............ 20· HgS 1.167 HgCl 2 = 0.1125 to 0.1375b
Mercuric chloride ... 0.5 HgS 1.167 HgCl. = 99.5
Mercuric oxide, oint-
ment of .......... 10 HgS 0.931 HgO = 0.9 to 1.1
Mercury, ammoni-
ated ............. 0.5 HgS 0.8622 Hg = 78 to 80
Mercury, ammoni-
ated, ointment of. 1.5 HgS 0.862 Hg = 7.1 to 8.7
N.F.
Bismuth, glycerite of 3.0 Bi 2S. 0.9063 Bi 20 3 = 12.5 to 13.5
.
• Number of tablets .
• Grams per tablet.
Exercise 7
Determination of the Purity of Calcium Glycerophosphate.-
The calcium is precipitated as oxalate, ignited, and weighed as
oxide.
Object.-Assay of Calcium Glycerophosphate.
Materials Required.---O.4 Gm. of calcium glycerophosphate.
20 cc. of 5 per cent acetic acid.
Ammonium oxalate T.S. (3.5 Gm. ammonium oxalate in 100 cc.).
Procedure.-l. "Dry about 0.4 Gm. of Calcium Glycerophosphate to
constant weight at 130°C., weigh accurately, dissolve in 20 cc_' of an aqueous
solution of acetic acid 1 in 20, and add 30 cc. of distilled water. Heat the
mixture to boiling, and add an excess of ammonium oxalate T.S."
C3H~(OH)2CaP04 + 2CHaCOOH---+Ca(CHaCOO)2 +
210.15 CaH 5 (OH)2H 2PO 4
Ca(CHaCOO)2 + (NH4)2C20C-+CaC204 + 2CHaCOONH 4
CaC 20c-+CaO + CO 2 + CO
56.08
Exercise 8
Determination of the Aluminum Content and Purity of Alulll.-
The aluminum is precipitated as hydroxide, ignited to oxide,
and weighed.
Object.-Assay of Alum.
Materials Required.-l Gm. of alum.
1 Gm. of ammonium chloride.
Ammonia T.S.
Procedure.-" Dissolve about 1 Gm. of Alum, accurately weighed, and
about 1 Gm. of ammonium chloride in 250 cc. of distilled water. Heat the
solution to boiling, and Mid a slight excess of ammonia T.S. to precipitate
aluminum hydroxide. Collect the precipitate on a filter, wash thoroughly
with hot distilled water, dry, ignite strongly, and weigh. The weight of
the aluminum oxide so obtained, multiplied by 8.894, indicates its equivalent
in Al'NH.(S04)2.12H 20 and when multiplied by 9.307, indicates its equiva-
lent in AlK(SO.):.12H 20."
Ammonium chloride is added to the dissolved alum to prevent
the formation of the colloidal form of aluminum hydroxide and
to prevent the precipitation of other hydroxides of metals,
as magnesium, which may be present,as- impurity. Ammonia
water is added to precipitate the aluminum as hydroxide. The
ammonia water should be freshly distilled, since upon standing
in glass containers it dissolves silica, the presence of which leads
to high re~mlts, the silica being precipitated and retained in the
precipitate. The ammonia water should be added in very slight
excess, since aluminum hydroxide is slightly soluble in strong
solutions of ammonia. The precipitation is conducted in boiling
solution to convert any colloidal aluminum hydroxide into large
particles and to secure a coarse-grained precipitate. The solution
should not be boiled after complete precipitation, for ammonium
salts become acid in reaction upon prolonged boiling due to loss
of ammonia, and the resulting acid solution would dissolve some
aluminum hydroxide. Aluminum hydroxide forms a slimy
precipitate difficult to wash. It is most easily washed by decan-
tation, using a hot wash liquid prepared by adding a drop of
ammonium hydroxide ~o hot distilled water. As much of the
supernatant liquid should be passed through the filter as possible
after the third washing before transferring the precipitate to the
filter, since the nature of the precipitate renders filtration very
GRA VIMETRIC METHODS 51
Sample,
Fac-
Substance Om. or Residue Official requirement, per cent
tor
cc.
- - - ---
U.S.P.
Alum, ammoniUDl ....... 1.0 AhO. 8.894 AINH.(SO.),.12H,O = 99.5
Alum, ammoniuOl, exsic-
cated ........•....... 0.5 AhO. 4.653 AINH.(SO.), '" 96.5
Alum, potassium ........ 1.0 AhO. 9.307 AIK(SO,),.12IhO - 99.5
Alum, potassium, exsic...
cated ................ 0.5 AhO. 5.066 AIK(SO.), = 96.5
Bismuth subcarbonate ... 1.0 BisO. ...... BhO. = 90
Bismuth subgallate ...... 1.0 Bi,O. ...... Bi,O. = 52 to 57
Bismuth subnitrate ..•... 1.0 BitO. ...... .BhO, - 79
Bismuth subsalioylate .•. 1.0 BhO. ...... BhO, - 62 to 66
Calcium creosotate ...... 0.2 CaO ...... CaO = 40 to 50
Zinc ac.tate ............ 1.0 ZnO 2.254 (CH,COO),Zn ~ 83.16 to 87.32
Zinc chloride ............ 1.0 ZnO 1.674 ZnCh - 95
Zinc oxide, ointment of .. 2.0 ZnO ...... ZnO = 19 to 21
Zinc suifate ............. 1.0 ZnO 1.984 ZnSO. = 55.86 to 58.63
N.F.
Aluminum acetate, solu-
tion of ............... 5.0 AhO. 4.0031 AI(C.H,O.,. = 4.8 to 5.8 W IV
Aluminum chloride ...... 0.5 AhO. 4.7369 AICIa.6H,O = 95
Aluminum chloride, solu-
tion of. .............. 5.0 AhO. 4.737 AlCla.6H,O = 22.5 to 27.5WIV
Aluminnm subacetate,
solution of ............ 5.0 AbO. 3.1788 Al(C,HaO,hOR = 7.5 to 8.5 W IV
Aluminum sulfate ....... 0.5 Al,O, 6.537 Alo(S04) •. 18H,0 = 99.5
Bismuth magna ....•.... 10.0 BilO. ...... Bi,O. = 5.6 to 6.2WIV
Bismllth subcarbona.te,
tablets of ............. 3.0- Bi,O. ...... Bi,O. = 83 to 97 b
Bismuth SUbgallate, tab-
lets of ••••••••• ••••••• a.o· Bi,O. ...... Bi,O. = 48 to 6]0
Bismuth subnitrate, tab-
lets of ................ 3.0· BilO. ...... BhO. = 73 to 85'
Bismuth subsalicylate.
ampuls of ............. 1.0· BisO. ...... BhO, - 57.6 to 70.4'
Calcium glycerophosphate 0.4 CaO 3.7473 CaC,H.(OH),PO. -= 98
Manganese citrate. soluble 0.5 Mn.O. 2.3728 [C.H •. OR(COO).],Mn. = 48 to 52
Manganese glycerophos-
phate ................ 0.5 Mn.O, 2.95 MnC,H.(OHhPO. = 98
Zinc phenolsulfonate ..•. 2.0 ZnO 6.8284 Zn(C,H.OSO.) •. 8H,O = 99.5
Exercise 9
Determination of the Magnesium in a Magnesium Salt.-The
magnesium is precipitated as magnesium ammonium phosphate,
washed, dried, ignited to pyrophosphate, and weighed.
Object.-Assay of Solution of Magnesium Citrate for Mag-
nesium Oxide.
Materials Required.-lO ee. of solution of magnesium citrate.
2 cc. of hydrochloric acid.
20 ce. of sodium phosphate T.S. (12 Gm. NazHPO. in 100 cc. of distilled
water).
Stronger ammonia T.S. (at least 27 per cent NH.).
Ammonia T.S. (9 to 10 per cent NH.).
Procedure.-l. "Transfer to a beaker of about 200-cc. capacity exactly
10 ee. of Solution of Magnesium Citrate which has been previously freed
GRAVIMETRIC METHODS 53
from excessive carbon dioxide by repeatcd pouring. Add 100 cc. of dis-
tilled water, 2 cc. of hydrochloric acid, 20 cc. of sodium phosphate T.S.,
and 2 drops of methyl red T.S. Add ammonia T.S a few drops at a time
with constant stirring until the solution becomes faintly yellow. Allow the
mixture to stand for ten minutes, add 40 cc. of stronger ammonia T.S. with
constant stirring, and allow the mixture to stand for two hours or over night."
Sample,
Official requirements,
Substance Gm. or Residue Factor
per cent
co.
--
-
U.S.P.
Magnesium cit-
rate, solution
of ............ 10.0 Mg2P 2Or 0.3621 MgO = 1.6 to 1.9W IV
Magnesium sul-
fate ..... " ... 1.0 Mg~20r 1.081 MgSO. = 99.5
Sodium phos-
phate ......... 0.3 Mg 2P 2Or 1.275 Na.HPO. = 98
Sodium phos-
phate, exsic-
cated ......... 0.2 Mg 2P 2Or 1.275 Na,HPO. = 98
N.F.
Magnesium sul-
fate, ampuls of 0.20 Mg 2P 2Or 2.2138 MgSO.7H 20 = 95 to 105~
Sodium phos-
phate, solution
of ............ 5.0 Mg 2P 2Or 1.275 Na,2HPO. = 39 to 41 W IV
• Weight of ingredient Bought.
b Per cent of labeled amount.
Sample,
Substance Gm. or Residue Official requirement. per cent
ee.
U.S.P.
Collodion ............. 10.0 Pyroxylin Pyroxylin ~ 5.1 W IV
Camphor, liniment of .. 5.0 Cottonseed oil Camphor ~ 19 to 21
Camphor. spirit of. .... 25.0 Camphor dinitro- Camphor = 9.5 to 10 5 W IV
phenylhydrazide
Erythrityl tetranitrate, 0.25 Erythrityl tetra- C.H,(NO.)< = 47 to 53
diluted. nitrate
Gold chloride, R .•..... 0.2 Au Au = 47
Iodine, compound, 80lu-
tion of (for KI) ...... 5.0 KI KI = 9.5 to 10.5 W IV ....
Iodine, tincture of (for
KI) ................... 5.0 KI KI = 4.5 to 5.5WIV
Iodine. tincture of, mild
(for NaI) ........... 5.0 Nal NaI = 2.1 to 2.5W IV
Molybdic anhydride, It. 0.5 PbMoO. MoO, = 99.5
Palladous chloride, R .. 0.2 Pd Pd = 59
Platinic chloride, R .... 0.5 Pt Pt = 37
N.F.
Camphor, ampule of ... 5.0 Ampul oil Camphor = 93 to 103&
Phenolphthalein, tahlets
01 .................. 0.65" Phenolphthalein Phenolphthalein = 92.5 to 107.5&
5. A volumetric flask calibrated to contain 100 cc. at 25°C. and 760 mm.
barometric pressure is used at 18°C. and 746 mm. barometric pressure.
Calculate the volume of water contained in the flask at the temperature
and pressure at which it is used.
HCl:NaOH::0.03647:x
(1)
HCI H++ CI-
(2) + +
NaOH OH- + Na+
~ il(3) 11(4)
HOH NaCI
Upon mixing the two solutions some Na+ and CI- ions unite
forming NaCl molecules-reaction (4). Water is only slightly
70 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
ionized, so nearly all of the H+ ions and OH- ions unite to form
HOH molecules-reaction (3). The removal of H+ and OH-
ions in reaction (3) causes reactions (1) and (2) to proceed to
completion, so that if equivalent quantities of HOI and N aOH
are employed, the final solution will contain only HOH, a small
quantity of undissociated N aCI molecules and N a+ and Cl- ions.
If one of the products of a reaction is removed the reaction
proceeds to completion readily; e.g., when KNO a in solutio:p. is
treated with HCI solution the equilibria represented by: equations
(1) and (2) exist prior to their admixture.
(1)
KNO a K+ +NOa
(2) + +
HCI Cl- +H+
U(3) U(4)
KCl HNO a
Color
Indicator pH range
Acid Alkaline
This table shows that methyl orange exhibits _its acid color,
pink, at a pH of 3.1 and its alkaline color, yellow, at a pH of 4.4,
while between these pH values the color undergoes transition
from one shade to the other. At a pH of 4.4 the solution is
slightly acid, since at neutrality pH = 7.
It would appear that an indicator which changes color exactly
at the neutral point, pH = 7, would be required in every case,
but this is not true. When a strong acid, such as hydrochloric
acid, is titrated with a strong base, like sodium hydroxide, the
change in concentration of hydrogen ion becomes very rapid as
72 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Two to four drops per 100 cc. of reaction solution are employed
in titrations.
The color ({hange is very sharp if too much indicator is not
used. Meth:lll orange is used frequently in the titration of strong
acids and strqng alkalies and especially in the titration of weak
bases, e.g., NH 40H. It is also a good indicator to use in the
titration of th'e salts of weak acids such as carbonates, borates,
sulfides, etc., with a strong acid, since in these cases the acids
liberated in t~e titration reaction are too little ionized to affect
the indicatorj It does not give the proper end point in the titra-
tion of alkal6ids or organic acids. This indicator should never
be employe~ in the titration of alcoholic solutions, hot solutions,
or very dilnte solutions.
Methyl Red. o-Carboxy-benzene-azo-dimethyl-aniline.-The
indicator(solution is prepared by dissolving 0.10 Om. of the dry
dye in 1.00 cc. of 95 per cent alcohol. Two to four drops of the
resulting solution are used per 100 cc. in titrations. Methyl
red in{licator is especially useful in titrating ammonia, weak
bases, ,and alkaloids, but it is not suitable for the titration of
weak organic acids.
Phenol Red. Phenol-sulfon-phthaJein.-The indicator solu-
tion ,Is prepared by triturating 100 mg. of the dry powder in a
mor-«ar with 14.5 cc. of 0.020 N NaOH until solution is complete
and <liluting the resulting solution to 250 cc. with recently boiled
distilled water. After the removal of any precipitate formed
upOll dilution, the solution is ready for use. In titrations, 3 to
6 drops of this indicator should be used for each 100 cc. of
sollJtion.
lfhenolphthalein indicator solution is prepared by dissolving
1 Gm. of phenolphthalein in 100 cc. of 95 per cent alcohol. Two
to three drops of this indicator should be used per'100 cc. of solu-
tion in titrations unless otherwise directed.
Phenolphthalein is an excellent indicator to use in the titra-
tion of weak organic and inorganic acids, most alkalies, and alkali.
salts, but it is not satisfactory for use in the titration of ammo-
nia, alkaloids, or cold solutions of carbonates and bicarbonates.
It fimctions well in alcoholic solutions.
Thymol Blue. Thymol-sulfon-phthalein.-The indicator solu-
tion is 'prepated by dissolving 40 mg. of the dry substance in
76 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Exercise 10
Preparation and Standardization of Hydrochloric Acid Solu-
tion.-Normal hydrochloric acid solution may be standardized
against pure sodium carbonate, standard solution of sodium
hydroxide, or gravimetrically by precipitating and weighing the
chloride ion as silver chloride.
Object.-To Prepare and Standardize Normal Hydrochloric
Acid.
Materials Required.-Hydrochloric acid.
4 Gm. of anhydrous sodium carbonate.
Procedure.-l. Dilute 95 cc. of hydrochloric acid with sufficient distilled
water to make 1,000 cc., and mix thoroug}lly.
When titration is complete, read the burette accurately and record the
volume of acid used in the titration.
Assuming that a sample of sodium carbonate weighing 1.6250
Gm. required 30.20 cc. of acid in the titration, the calculations
are made as follows:
If the acid were exactly normal, according to the definition of
.
a normaI soIutlOn, 1,000 cc. woul neutralIze
d · 1 mole 2Na 2CO a =
water into a dry 1,000 cc. flask, fill to the mark with 1.0152 N
Hel, mix the solution well, and verify the normality of the solu-
tion by titratiQn agamst weighed samples of sodium carbonate.
Volumetric solutions of hydrochloric acid may be standardized
gravimetrically by determining the amount of chloride ion
present as silver chloride, as described under gravimetric deter-
mination of ch~orides, using 10 cc. portions of the acid as samples.
Ten cubic centimeters of N Hel is equivalent to 1.4334 Gm. of
Agel. If a 10 cc. portion of acid is found to yield 1.4634 Gm. of
Agel, the acid is 1.4634/1.4334 = 1.0210 normal.
Solutions of hydrochloric acid may also be standardized by
titration against standard solutions of KOH or NaOH. Thus _ii
25.20 cc. of 0.9505 N NaOH is required to exactly neutralize
25.00 ce. 9f acid, the factor of the acid is 25.202~0~·9505 = 0.9531
normal.
The normal solution is too strong for many assay procedures,
so 0.5 N, 0.2 N, 0.1 N, etc., solutions are employed. These may
be prepared by dilution of the normal solution in the proper _
ratio, but the resulting solution should always be restandardized.
Standard solutions of hydrochloric acid preserved in tightly
stoppered, alkali-free, glass bottles retain their strength in-
definitely.
Exercise 11
Preparation and Standardization of Alkali Solutions.-Solu-
tions of sodium hydroxide or potassium hydroxide may be
standardized against standard solution of hydrochloric or sul-
furic acid or by titration against an accurately weighed quantity
of pure potassium bitartrate or potassium biphthalate.
Object.-To Prepare and Standardize Normal Sodium Hydrox-
ide Solution.
Materials Required.-About 50 Gm. of sodium hydroxide.
A saturated solution of barium hydroxide.
A standardized solution of hydrochloric acid.
Procedure.-l. Weigh about 50 Gm. of sodium hydroxide on a rough
balance and dissolve it in about 1,000 cc. of distilled water. Add slowly
with stirring a sat~rated solution of pure barium hydroxide until no further
precipitation occurs (2 to 3 cc.). Allow the precipitate to subside for about
10 hr. and decant the liquid through a filter into a hard glass bottle or a
82 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
bottle the inside of which has previously been coated with paraffin. Close
the bottle tightly with a rubber stopper provided with a soda-lime tube.
More than a mole, 40.00 Gm., of sodium hydroxide is weighed
out, since it is hygroscopic, and if only a mole were used the result-
ing solution would be below normal strength. The solution is
treated with barium hydroxide to precipitate any carbonate
formed through the action of carbon dioxide on the sodium
hydroxide. The solution is preserved in a tightly stoppered
bottle fitted with a soda-lime tube to protect it from the carbon
dioxide of the air. Solutions which contain carbonate are not
suitable for titration with phenolphthalein as indicator, but when
methyl orange is used the results are the same as if all the sodium
were present combined as hydroxide.
2. Accurately measure 30 cc. of normal hydrochloric or normal sulfuric
acid, dilute with 50 cc. of carbon dioxide-free distilled water, add 2 drops of
phenolphthalein T.S., and titrate with the sodium hydroxide solution to the
production of a permanent pink color. If the end point is passed in the
titration, add a few cubic centimeters more of acid and again titrate to
the end point. Titrate several portions of the alkali and from the mean of
the results calculate the normality of the sodium hydroxide solution.
A large volume, about 30 cc., of solution-is used for each
titration to minimize error from measurements. Every precau-
tion should be taken to insure the correct ineasurerhent of the
volume of solutions. The burettes should be cleaned, freed from
air bubbles before titration, and read with the great~st possible
accuracy.
The solution can be made exactly normal by dilution in the
same manner as that explained under the preparation of normal
hydrochloric acid. Assuming that 30.00 cc. of alkali solution
required 30.15 cc. of 1.0119 N HCI, the factor of the sodium
hydroxide solution would be
30.15 ;01.0119 = 1.0170.
ALKALIMETRY
Alkali hydroxides and carbonates, etc., are usually titrated
directly with standard solutions of hydrochloric or sulfuric
acid using methyl orange as indicator. Phenolphthalein and
methyl red when used as indicators in such titrations are affected
by the acidic carbon dioxide liberated during titration so that the
end point appears before neutralization is complete. If phenol-
phthalein is used as indicator, carbonates must be removed by
precipitation before titration, or the titration mixture must be
boiled to expel the carbon dioxide formed during titration.
Direct titration is conducted by adding a standard reagent
solution in measured quantity to a substance in solution until the
end point, as shown by a change of indicator color, is reached.
Substances which are insoluble in water or which do not yield
a sharp end point that coincides with the stoichiometric point
upon direct titration are titrated residually.
Residual titration is conducted by treating the substance under
analysis with an amount of standard solution knorvn to be in
excess of that actually required to react with it completely;
the amount of standard solution in excess is then determined by
titration with another standard solution.
Exercise 14
Object.-Assay of Sodium Bicarbonate.
Materials Required.-About 8 Gm. of sodium bicarbonate.
Normal sulfuric acid.
Procedure.-" Dry about 3 Gm. of Sodium Bicarbonate to constant_weight
over sulfuric acid, weigh accurately, mix it with 25 cc. of distilled water, and
titrate with normal sulfuric acid, using methyl orange T.S. as the indicator.
Each cubic centimeter of normal sulfuric acid is equivalent to 0.08400 Gm.
of NaHCO a."
Exercise 16
Object.-Assay of Sodium Hydroxide.
Materials Required.-1.5 Gm. sodium hydroxide.
Normal sulfuric acid.
Procedure.-l. "Dissolve about 1.5 Gm. of Sodium Hydroxide, accu-
rately weighed, in about 40 cc. of recently boiled and cooled distilled water.
Cool the solution to 15°C. and 'titrate with normal sulfuric acid, using
phenolphthalein T.S. as the indicator. At the discharge of the pink color
of the indicator, record the volume of acid solution required."
2(84.00)
The method of calculation is as follows: If a 1.0000 Gm.
sample of NaOH r.equired 20.80 cc. of N H 2S0 4 to titrate to the
end point with phenolphthalein indicator and an additional
0.95 cc. of N H 2S0 4 to titrate to the end point with methyl
orange indicator, the total alkali calculated as NaOH would be
20.80 + ~. ~go~ 0.0400 X 100 = 87 per cent. The volume of
N H 2S04 required to titrate the NaHCO s, after the titration to
an end point with phenolphthalein, represents one-half of the
acid that would be necessary to neutralize the Na 2CO a originally
ALKALIMETRY 89
The sodium salicylate reacts with the added acid to form free
salicylic acid and sodium chloride as follows:
C 6H 4.OH.COONa + HCl~C6H4.0H.COOH + NaCl
160.04 138.05
gO QUANTITATIVE PHARMACEUTICAL CHEMISTRY
2. "Transfer the contents of the beaker to a small separator, and draw off
the aqueous layer into a small flask. Wash the ethereal layer once with 5 CC.
of distilled water, and add this to the aqueous layer. Add 20 cc. of ether to
the combined aqueous solutions, and mix intimately. Continue the titration
with vigorous shaking until a permnnent, pnle green color is produced in the
aqueous layer. Each cubic centimeter of half-normal hydrochloric acid is
equivalent to 0.08002 Gm. of C eH 4.OH.COONa."
II
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92 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Exercise 17
The salt is heated slowly at first, since the sample swells and
fuses with concomitant decomposition. If strong heat is applied
in the initial stages of ignition, there may be loss of a portion of
the sample through decrepitation or spattering. After the mass
in the crucible is partially charred and white fumes are no longer
evolved, it is ignited to dull redness. If heated too strongly or
if the flame comes in contact with the carbonized mass, the alkali
carbonate may be converted into the oxide.
2. "After allowing the carbonized mass to cool, disintegrate it with the
aid of a stout glass rod and transfer thc mass and crucible to a beaker. Add
50 cc. of distilled water and 50 cc. of half-normal sulfuric acid, cover the
beaker with a watch glass and boil the contents for thirty minutes. Then
filter the solution and wash the residue with hot distilled water until the
washings cease to redden blue litmus paper. Now determine the residual
acid in the cooled filtrate by titration with half-normal sodium hydroxide,
using methyl orange T.S. as the indicator. The volume of half-normal
sulfuric acid consumed, multiplied by the proper equivalent of the salt,
represents the quantity of the salt present in the quantity taken."
Exercise 19
Object.-Assay of Magnesia Magma.
Materials Required.-5 Gm: of magnesia magma.
Normal sulfuric acid.
Normal sodium hydroxide.
Procedure.-" After thorough agitation, place about 5 Gm. of Magnesia
Magma in a tared flask, stopper, and weigh accurately, add 25 cc. of normal
sulfuric acid, and after solution is complete, titrate the excess of acid with
normal sodium hydroxide, using methyl red T.S. as the indicator. Eaoh
cubic. centimeter of normal sulfuric acid is equivalent to 0.02917 Gm. of
Mg(OH)2,"
Exercise' 20
Object.-Assay of Methenamine.
96 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Exercise 21
Object.-Assay of Solution of Ammonium Acetate.
Materials Required.-25 cc. of solution of ammonium acetate.
Sodium hydroxide, T.S.
Normal sulfuric p,cid.
Normal sodium hydroxide.
Procedure.-"Transfer 25 cc. of Solution of Ammonium Acetate to a
distilling flask, dilute with 75 cc. of distilled water, add 50 cc. of sodium
hydroxide T.S., and distil the liquid until all of the ammonia has been
driven over (about 100 cc. of distillate), receiving the distillate under the
surface of 50 cc. of normal sulfuric acid contained in a flask. Titrate the
excess of acid with normal sodium hydroxide, using methyl red T.S. as
the indicator. Each cubic centimeter of normal sulfuric acid is equivalent
to 0.07706 Gm. of CH,.COO.NH 4."
The NaOH reacts with the ammonium acetate liberating NHa
and combining with the acetic and carbonic acids to form non-
volatile compounds. The distilling flask should be connected
to the condenser at once after adding the NaOH to prevent loss
of the volatile NH a. The NHa formed in the reaction,
CH aCOONH 4 + NaOH~CHaCOONa + NHa + H 0, 2
77.06
distils with water when the flask is heated. The NHa is con-
ducted into a receiving flask which contains an excess of N
H 2S0 4 • The condenser should be fitted tightly with an adapter
~n such a manner that the distillate will be collected beneath the
surface of ,the standard acid. This is done to prevent loss of
NHa from the distillate. As soon as the NHa in the distillate
comes into the receiving flask, it combines with the H 2S0 4 to
forni (NH 4 )S04,
2NHa + H2S04~(NH4)2S04
17.03 132.14
The excess acid is then determined by titration with standard
alkali. "
Questions and Problems
1. Why is methyl red rather than phenolphthalein used in this assay?
2. Write equations for the reactions that occur in the assay of: (a)
aromatic spirit of ammonia, (b) ammonium bromide in tablets of three
bromides, (c) acid ammonium valerate, (d) ammonium carbonate.
98 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
opening so that the free flame will come in direct contact with the bottom
of the flask. Heat below the boiling point for about 10 min. or until frothing
has ceased and then raise the temperature and boil the mixture until the
latter acquires a pale straw color or is nearly colorless.
The proteins and other organic matter are oxidized by the
sulfuric acid-potassium sulfate mixture, leaving the nitrogen
combined as ammonium sulfate. If foaming occurs at first,
it can be prevented, for the most part, by dropping a small piece
of paraffin into the flask. The time necessary for the oxidation
of the compounds depends upon their nature, from Y2 t<J 12 hr.
heating being required by different compounds and mixtures.
A small crystal of copper sulfate or a globule of mercury may be
added to the digestion mixture to catalyze the oxidation.
6. Cool the flask, add about 250 cc. of distilled water, and cautiously
add a 30 per cent solution of sodium hydroxide until the contents of the
flask are distinctly alkaline. Use phenolphthalein added to the mixture
as indicator. Connect the flask at once to the Kjeldahl trap, condenser,
and receiver as illustrated in Fig. 14, so that the lower end of the condenser
dips beneath the surface of 25 cc. of 0.1 N sulfuric acid contained in the
receiving flask. Distil the mixture until about 100 cc. of distillate is
obtained.
In making the mixture alkaline, it should be borne in mind
that the pink, alkaline color of the phenolphthalein is destroyed
by a large excess of alkali. A few pieces of granutar zinc or
porous plate placed in the flask prior to distillation will prevent
bumping. The alkali liberates the ammonia from the ammonium
sulfate, and upon distillation the ammonia gas is driven over and
collected in the standard acid. In the analysis of compounds
containing a high percentage of nitrogen, all of the standard acid
may be neutralized before the whole of the ammonia has distilled.
If from 2 to 3 drops of methyl red or cochineal indicator are
added to the standard acid before the distillation is started, the
color of the indicator will show whether all the acid has been
neutralized, and in case it has, more standard acid can be placed
in the receiver without an appreciable loss of ammonia. The
Kjeldahl trap in the apparatus prevents liquid from the distilla-
tion flask from being carried over mechanically.
7. Add methyl red or cochineal indicator solution to the distillate and
titrate the excess acid with 0.1 N sodium hydroxide solution. Calculate
the percentage of nitrogen in the alcohol-soluble solids.
ALKALIMETRY 103
--- --_ - - -
U.S.P.
Alnmonia, aroma-
tic spirit of (for
total NH,) ... 10 M.R. 0.5 0.008515 NH, = 1.7 to 2.1
Ammonium ace-
tate, solution of 25 M.R. 1.0 0.07706 CR,COO.NR. = 6.5 to 7.5 W IV
Ammonium car-
bonate ... , ... , 2 M.O. 1.0 0.01703 NH, = 30-32
Effervescent pow-
ders, compound 2 Pp. 0.5 0.04201 NaHCO, = 23 to 27
Glyceryl trini-
trate, tablets of. 0.05 a M.R. 0.02 0.001514 C,H,(NO,)' = 87.5 to 112.5'
Magnesia magma. 5 M.R. 1.0 0.02917 Mg(OH), = 7 to 8.5
Magnesium car-
bonate ........ 1 M.O. 1.0 0.02016 MgO = 39.2 to 41.5
Magnesium oxide. 0.5 M.O. 1.0 0.02016 MgO = 96
Magnesium oxide,
heavy ......... 0.5 M.O. 1.0 0.02016 MgO = 96
Methenamine .. . , 1 M.R. 1.0 0.03503 (CH,),N. = 99
Potassium acetate 2 M.O. 0.5 0.04906 CR,COOK = 99
Potassium and so-
dium tartrate .. 2 M.O. 0.5 0.05254 KNaC.H.O, = 99
Potassium citrate. 2 M.O. 0.5 0.05106 K,C.H,O,.H,O = 99
Sodium acetate .. . 2 M.O. 0.5 0.04102 CH,COON" = 99
Sodi urn ci tm te ... 1.5 M.O. 0.5 0.04301 Na,C,H,O, = 99
Zinc oxide . . , ... , 1.5 M.R. 1.0 0.04069 ZnO = 99
Zinc stearate ..
N.F.
.. 1 M.R. 0.1 0.004069 ZnO = 13 - 15.5
Ammonium bro-
mide in tablets
of three bro-
mides ...... ,. 0.6· M.R. 0.5 0.04898 NH.Br = 30.8 to 35.8'
Ammonium valer-
ate, acid .. 1.5 M.R. 0.5 0.05955 C.H.COONH. = 62 to 67
Calamin.~. Iwe-
pared ....... 1.5 M.O. 1.0 0.04069 ZnO = 98
Iron and ammon~
ium acetate.
solution of. .... 25 M.R. 0.5 0.008515 NH. = 0.6 to 0.8W IV
Ichthammol (for
NR,) ....... 5 M.R. 0.5 0.008515 NR, = 2.5
Lithium carbo~~
ate ............ 1.5 M.O. 1.0 0.03694 Li,CO, = 99
Lithium citrate ... 2 M.O. 0.5 0.03498 C,H •. OH.(COOLJla = 98.5
Methenamine,
ampuls of ...... 1 M.R. 1.0 0.03503 (CR,),N. = 95 to 105'
Methenamine,
tablets of. ..... 1· M.R. 1.0 0.03503 (CH,),H. = 94 to 106'
Methenamine and
sodium biphos- \"
phate, tablets
of ............. 0.25· M.R. 0.5 0.01752 (CH,),N. = 92.5 to 107.5'
Zinc oxide in mild
resorcinol paste 1 M.O. 1.0 0.04069 ZnO = 24 to 26
Zinc oxide in
strong resor-
cinol paste .. 1 M.O. 1.0 o 04069 ZnO = 19 to 21
ACIDIMETRY
Acids are estimated quantitatively by methods analogous to
those employed in alkalimetry, namely, by directly titrating an
exact quantity of the acid or acid salt with standard alkali
solution or by adding an excess of the latter and· determining the
amount in excess by. residual titration with standard acid solu-
tion: Direct titration is employed whenever practicable, since
it is easier and requires fewer burette readings.
In assaying acids, the quantity of acid to be taken should be
such that about 30 to 40 cc. of the alkali solution will be con-
sumed. As a general principle, it is recommended that the
normality of the acid to be titrated should be approximately
the same as that of the titrating medium. Except when other-
wise directed, the liquid to be titrated should be brought to room
temperature before titration, as many indicators give different
values at different temperatures. For most of the inorganic
acids, methyl orange, methyl red, phenolphthalein, or litmus
can be used as indicators, but the alkali must be standardized
with the particular indicator used. For organic acids, phenol-
phthalein is always used.
DIRECT TITRATION METHODS
Exercise 23
Object.-Assay of Hydrochloric Acid.
Materials Required.-3 cc. of hydrochloric acid.
Normal sodium hydroxide.
Procedure.-"Weigh accurately about 3 cc. of Hydrochloric ACHl III a
tared, glass-stoppered flask. Dilute with about 25 cc. of distilled water
and titrate with normal sodium hydroxide, using methyl red T.S. as the
indicator. Each cubic centimeter of normal sodium hydroxide is equivalent
to 0.03647 Gm. of He!."
Concentrated acid solutions are weighed in glass-stoppered
flasks to prevent loss of dissolved gases in some cases and to
105
106 QUANTITATIVE PHARMA(;1!Ju'1'lI.-'AL CHEMISTRY
98.08 2(40.00)
Since sulfuric acid is a dibasic acid and each mole is equivalent
to 2 moles of the monoacidic base, NaOH, the H 2S0 4 equivalent
of 1 cc. of 1 N NaOH will be 98.08/2 X 1,000 = 0.04904. Calcu-
late the per cent of H 2S0 4 in the sample assayed.
Questions and Problems
1. What indicator solutions are suitable for use in the assay of diluted
sulfuric acid?
2. List a number of other official diluted acids, which are assayed by a
similar procedure, with the indicators used in each.
3. If the sample of H 2S0 4 assayed in this exercise had a specific gravity of
1.0640, what would be the per cent by weight?
4. Calculate the sodium carbonate and ammonium hydroxide titers of the
acid assayed in this exercise.
Exercise 26
Object.-Assay of Boric Acid.
Materials Required.-2.5 Gm. of boric acid.
100 cc. of glycerin.
Normal sodium hydroxide.
Procedure.-" Dry about 2 Gm. of Boric Acid to constant weight over
sulfuric acid, weigh accurately, and dissolve the dried Acid in 100 cc. of a
mixture of equal volumes of glycerin and distilled water, previously neutral-
ized to phenolphthalein T.S. Titrate with normal sodium hy_droxide, using
phenolphthalein T.S. as the indicator. Discharge the pink color by the
addition of 50 cc. of glycerin, neutralized to phenolphthalein T.S., and
again titrate until the pink color reappears. Each cubic centimeter of
normal sodium hydroxide is equivalent to 0.06184 Gm. of HaBO •. "
Exercise 26
Object.-Assay of Tablets of Sodium Salicylate.
Materials Required.-20 tablets of sodium salicylate.
Diluted hydrochloric acid.
About 100 cc. of ether.
2 cc. of neutral alcohol.
Ferric chloride, T.S.
0.1 N sodium hydroxide.
Procedure.-l. "Weigh not less than 20 of the Tablets, reduce them to a
fine powder without an appreciable loss, and transfer an aliquot portion,
equivalent to about 0.3 Gm. of sodium salicylate, to a separatory funnel.
Add 25 cc. of distilled water and a slight excess of diluted hydrochloric acid,
and completely extract the liberated salicylic acid with ether. Transfer
the ethereal solution to a suitable flask and distil off most of the ether, being
careful not to volatilize the salicylic acid, and allowing the last few cubic
centimeters to evaporate spontaneously."
The tablets are weighed before powdering so that the average
weight per tablet can be computed. When Hel is added, salicylic
acid is set free as indicated by the following equation:
ACIDIMETRY 109
C aH 4(OH)COOH + NaOH~CaH40HCOONa + H 0 2
138.05 160.04
One cubic centimeter of 0.1 N NaOH is equivalent to
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ACIDIMETRY 113
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114 QUANTITATIVE PHARMACEUTICAL CHEMISTR¥
Amount
used, Indi-
Nor- Equiva- I
Substance mality lent of Official requirement, per cent
Gm. or cator
of alkali 1 cc.
cc .
• --- - _ - ,
U.S.P.
Acid, acetylsalicylic 1.5 Pp. 0.5 0.04502 C.H.O(CH,CO)COOH = 99.5
Acid, lactic ........ 2.5 Pp. 1.0 0.09005 CH,CHOHCOOH = 8S,to 90
Acid, sulfuric aro-
matic ........... S.O M.O. 1.0 0.04904 H,SO. = 19 to 21 W IV
Chloral hydrate ... 4.0 Pp. 1.0 0.1654 CChCHO.H,O = 99.5
Formaldehyde,
solution ....... . 3.0 B.T.B. 1.0 0.03002 HCHO = 37
Methyl salicylate .. 2 Pp. 0.5 0.07603 C.H •. OH.CO,CH, = 98
N.F.
Acetylsalicylic acid,
tablets of. ...... O.;7a Pp. 0.1 0.01801 C.H •. OCOCH,.COOH =:92.5
to 107.5'
Ethyl acetate ..... I.S Pp. 0.5 0.04403 CH,COO.C,H. = 99
Formic acid, spirit
of. .. .. , " 10 Pp. 0.1 0.004602 HCOOH = 0.95 to 1.0SWIV
PRECIPITATION METHbD~
Exercise 31
and
Exercise 32
Amount Equiva-
Official require-
Substance used, Gm. lent of
ment, per cent
or cc. 1 cc.
U.S.P.
Mass of mercury. . . . . . . .. . .. . 0.5 0.01003 Hg = 32 to 34
Mercuric oxide, yellow ........ . 0.5 0.01083 HgO = 99.5
Mercuric salicylate ........... . 0.5 0.01003 Hg = 54 to 59.5
Mercuric succinimide ....... . 0.5 0.01003 Hg = 49.5 to 51
Mercury, oleate of. . . . . . . . .. .. 0.75 0.01083 HgO = 24 to 26
Mercury., ..... , ..... , ..... " .. 0.4 0.01003 Hg = 99.5
Mercury with chalk ... , , ... , . , . 1.0 0.01003 Hg = 37 to 39
Ointment, mercurial, mild .. , . , . 1.0 0.01003 Hg = 29 to 31
Ointment, mercurial, strong, ... 1.0 0.01003 Hg = 49 to 51
Silver ni-trate .... , .. , ..... , .. , 0.8 0.01699 AgNO. = 99.8
Silver nitrate, toughened, .. , ... 0.8 0,01699 AgNO. = 94.5
Silver protein, mild. , ... , . , , .. , 1.0 0.01079 Ag = 19 to 25
Silver protein, strong ... , .. , ... 2.0 0.01079 Ag = 7.5 to 8.5
N.F.
Arsenic and merouric iodides,.
solution of (for HgI 2 ) • • • • . • • • 25 0.02272 HgI 2 = 0.95 to 1.05
Mercuric oxide, red. . ..... , ... 0,5 0.01083 HgO = 99.5
Mercuric salicylate, ampules of 0.5 a 0.01003 Hg = 51.0 to 62.4 b
Mercuric succinimide, ampuls of I 0.25" 0.01003 Hg = 47.7 to 52.8b
equivalent to 0.01140 Gm. of pure Ag, what would be its equivalent of Hg,
HgI •• HgO, Hg(NO.) •• AgNO., and Ag.O?
3. Give a method for the assay of metallic mercury. Explain each step
in the procedure and write equations for all reactions.
4. What must be the normality of a solution of NH 4SON so that each
cubic centimeter shall be equivalent to 1 mg. of silver?
o. Write equations for the reactions that occur in the assay of: (a) yellow
mercuric oxide, (b) mercuric succinimide, (c) mercuric iodide in solution of
arsenic and mercuric iodides.
3. How might all of the excess silver nitrate solution be freed from the
precipitate and titrated?
4. Name several official chlorides assayed by the above method.
6. What must be the normality of a standard silver nitrate solution so
that each cubic centimeter will be equivalent to 1 mg. of chlorine?
Exercise 34
Object.-Assay of Ammonium Bromide.
Materials Required.-0.4 Gm. of ammonium bromide.
2 cc. of nitric acid.
2 cc. of ferric alum indicator.
50 cc. of 0.1 N silver nitrate.
0.1 N ammonium thiocyanate.
Procedure.-"Dry about 0.4 Gm. of Ammonium Bromide to constant
weight in a desiccator over sulfuric acid, and weigh accurately. Dissolve
it in about 50 cc. of distilled water, add 50 cc. of tenth-normal silver nitrate,
2 cc. of ferric ammonium sulfate T.S., and 2 cc. of nitric acid. Titrate the
excess of silver nitrate with tenth-normal ammonium thiocyanate. Each
cubic centimeter of tenth-normal silver nitrate is equivalent to 0.009796 Gm.
of NH 4Br. Each gram of Ammonium Bromide, previously dried, is equiv-
alent to not less than 101.1 cc. and not more than 103.0 of tenth-normal
silver ni trate."
The above assay is similar to that for chlorides, except that the
precipitated silver bromide need not be removed by filtration,
since it is less soluble than silver thiocyanate. I
The reactions and calculations are similar to those of the pre-
ceding assay. Write equations for all reactions involved and
calculate the per cent purity of the ammonium bromide.
Questions and Problems
1. How does the presence of excess silver nitrate tend to produce quanti-
tative precipitation of silver bromide?
2. How does the formation of insoiuble silver bromide force the reaction
to completion?
3. Why may the residual titration of excess silver nitrate be conducted
without removal 0{ the precipitated silver bromide?
4. Look up the solubility product of AgBr and calculate the solubility of
silver bromide.
5. Write all equations ionically.
Exercise 35
Object.-Assay of Syrup of Hydriodic Acid.
Materials Required.-25 cc. of syrup of hydriodic acid.
40 ce. of 0.1 N silver nitrate.
PRECIPITATION METHODS 125
5 cc. of nitric acid.
2 cc. of ferric alum indioator.
0.1 N ammonium thiocyanate.
Procedure.-"Place exactly 25 cc. of Syrup of Hydriodic Acid in a flask,
dilute it with 100 cc. of distilled water, add 40 cc. of tenth-normal silver
nitrate, agitate the mixture, add 5 cc. of nitric acid and heat the mixture on
a water bath until the preoipitate has acquired a bright yellow color. Cool,
add 2 cc. of ferric ammonium sulfate T.S., and determine the residual silver
nitrate by titration with tenth-normal ammonium thiocyanate. Each cubic
centimeter of tenth-normal silver nitrate is equivalent to 0.01279 Gm. of HI."
Exercise 36
Object.-Assay of Elixir of Three Bromides ..
Materials Required.-10 cc. of elixir of three bromides.
0.1 N silver nitrate .
. 2 cc. of nitric acid.
2 cc. of ferric alum indioator.
0.1 N ammonium thiocyanate.
126 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
F = a
bl
Cl
+ C2b + C3ba, etc.
2
Equiva-
Amount
lent of
used. Official requirement,
Substance 1 cc. of
Gm. per cent
0.1 N
or co.
_--
NH,SCN
U.S.P.
Acid hydriodic. diluted ...... '.' .. 5 0.01279 HI = 9.5 to 10.5
Acriflavine .................... . 0.25 0.003546 Cl = 13.3 to 14.3
Acriflavine hydrochloride ....... . 0.25 0.003546 Cl = 23 to 24.5
Ammonium bromide ....... ... . 0.4 0.009796 NH,Br = 99
Ammonium chloride .... . 0.1 0.005350 NH,CI = 99.5
Calcium chloride. R ........ . 2 0.0055.50 CaC]' = 74
Chloroform. liniment of. .. . ... 10 0.00398 CHCla = 40 to 45 W /V
Chloroform. spirit of. . . . . . . .. 5 0.00398 CHCla = 8.5 to 9.25 W /V
Oil of mustard. volatile. .. .. . . 4 0.004956 C,H,NCS = 93
Potassium bromide ............ . 0.4 0.01190 KBr = 99
Potassium nitrate .............. . 0.4 0.01011 KNO, .:, 99
Sodium bromide ............... . 0.4 0.01029 NaBr = 99
Sodium chloride ............... . 0.25 0.005845 NaCI = 99.5
Syrup of ferrous iodide ......... . 10 0.01548 FeI, = 6.5 to 7.5W/V
Syrup of hydriodic acid ......... . 25 0.01279 HI = 1.3 to 1.5W/V
N.F.
Ammonium bromide, elixir of ., 10 0.009796 NH,Br = 8 to 9W/V
Ammonium chloride. tablets of. 0.15· 0.00535 NH,CI = 92.5 to 107.5'
Ammonium iodide ............ . 0.5 0.01450 NH,I = 98
Bromides, five, elixir of . . , .. - ... . 10 0.0102 total bromides = 25 to 27 W /V
Bromides, three, elixir of, ....... . 10 0.01059 total bromides = 23 to 25 W /V
Bromides. three. tablets of. ..... . 0.6· 0.007992 Br = 70 to 81 b
Lithium bromide .............. . 0.35 0.008686 LiBr = 85 to 90
Potassium broIuide. elixir of . .... . 5 0.01190 KBr = 17 to 18W/V
Potassi urn chloride . ............ . 0.25 0.007455 KCI = 99
Potassium thiocyanate .. , ....... . 0.2 0.009716 KSCN = 99
Sodium hromide. elixir of. ...... . 5 0.01029 NaBr = 17 to 18W/V
Sodium bromide. tablets of ...... . 0.3" 0.01029 NaBr = 92.5 to 107.5b
Sodium chloride in isotonic solu-
tion of dextrose and. . ....... . 0.2" 0.005845 NaCI = 0.4 to 0.425W/V
Sodium chloride in ampuls of dex-
trose and ................... . 0.2· 0.005845 NaCI = 95 to 105 b
Sodium chloride. ampuls of ...... . 0.2" 0.005845 NaCI = 95 to 105 b
Sodium nitrite. tablets of ....... . 0.5" 0.02070 NaNO, = 91 to 109b
Sodium thiocyanate ... ......... . 0.2 0.008107 NaSCN = 98.5
Strontium bromide ............. . 0.5 0.01778 SrBro.6H,O = 98
,
Zinc iodide .................... . 0.5 0.01596
~
ZnI, = 98
R. = reagent.
a Amount of ingredient Bought.
b Per cent of the.labeled amount.
128 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
(1) Fe + 2HC1~FeCb + H2
or
(2) Fe + 2H+ + 2Cl-~Fe++ + 2Cl- + H2
Zero + 2( +) + 2( -) = 2( +) + 2( -) + zero.
Since Cl- is present on both sides of equation (2) the essential
reaction is Fe + 2H+~Fe++ + H 2. During the reaction,
the iron has changed (been oxidized) from a neutral atom to an
ion bearing two positive charges through the loss of 2 electrons,
and the 2 hydrogen ions have each gained 1 electron (been
reduced to molecular hydrogen).
If the ferrous ion is further oxidized to the ferric state, it
loses another electron:
Fe++----> Fe+++ + (-)
OXIDATION-REDUCTION METHODS 131
In the reaction
2Fe++ + Ck-~2Fe+++ + 2Cl-
each ferrous ion loses 1 electron which is gained by a chlorine
atQm, for a negative charge on an ion indicates that it has gained
an extra electron. In the above case, the ferrous ion has been
oxidized, since it lost an electron, and chlorine has been reduced
to chloride ion, since it gained an electron.
When ferric chloride is reduced by stannous chloride, the
following reaction takes place: 2FeCla + SnCh~2FeCb +
SnC1 4 , which written ionically becomes
2Fe+++ + Sn++~2Fe++ + Sn++++
2(55.84) 118.7
Each ferric ion gains one electron at the expense of the stannous
ions, each of which loses two electrons. The quantity of electric-
ity gained by the iron is 96,500 coulombs for every 55.84 Gm. of
iron reduced, and that lost by the tin is 2 X 96,500 coulombs
for every 118.7 Gm. of tin oxidized. The chloride ion is in the
same state of oxidation before as after the reaction, since it
undergoes no change of charge.
In most cases, the change of charge which an atom, ion, or
radical undergoes in an uxidation-reduction reaction is numeri-
cally equal to the change in valence, i.e.:
1. When ferrous iron is oxidized to the ferric condition, the
charge associated with the iron atom changes from two to three:
2Fe++ + 2H+~2Fe+++ + H2
and the valence also changes from two to three:
Cl Cl
/ /
2Fe + C1 2---2Fe-Cl
'" Cl '0> '" Cl
2. When potassium permanganate is reduced, the manganese
atom gains five negative charges:
Mn7(+)~M!l++ + 5(+)
132 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
o 0
/""-/
---+Mn S (See assay of FeS04 page 136.)
""-/~
o 0
3. Iodine-iodide ion
12 - 21-
Zero 2( -) + 2( + )
Exercise 37
Object.-To Prepare and Standardize 0.1 N Potassium
Permanganate.
Materials Required.-About 3.3 Gm. of potassium permanganate.
About 1 Gm. of reagent sodium oxalate.
Procedure.-l. "Dissolve about 3.3 Gm. of potassiul1t permanganate in
1000 cc. of distilled water in a flask and boil the solution for about fifteen
minutes. Stopper the flask and allow it to stand for at le!\'st two days before
filtering through asbestos."
Exercise 39
To Determine the Purity of Reduced Iron.-In this assay the
metallic iron is converted quaptitatively into ferrous ion and
estimated oxidimetrically by titration with potassium permanga-
nate solution.
138 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Exercise 40
The reasons for the various steps in the above assay have
already been given under the assay of ferrous sulfate. This
assay illustrates a case where an oxidizing agent, H 20 2, serves
as a reducing agent for KMn04 and is itself reduced. When
H 20 2 acts as a reducing agCent, 1 Gm.-atom of oxygen from each
mole of H 20 2 is capable of uniting with 1 Gm.-atom of oxygen
from the substance reduced (KMn04.) to form 1 mole of oxygen
gas:
2HO +0 (from oxidizing agent)--+H 20 +O 2
Equiva-
Amount
lent of
used, Official tequirement,
Substance 1 cc.
Gm. or per cent
0.1 N
ee.
KMn04
U.S.P.
Ferrous sulfate .......... 1 0.01519 FeSO. = 54.36 to 57.07
Hydrogen peroxide solu-
tion .................. 2 0.001701 H 20 2 = 2.5 to 3.5
Hydroxylamine hydro-
chloride, R ........... 0.1 0.003475 NH 20H.HCI = 95
.
Indigo carmine, R, '.' .... 0.3 0.01333 C 16 H,02N 2(S03Na). = 82
Iron, reduced ........... 1 0.005584 Fe = 90
Lead peroxide, R ........ 0.5 0.01196 Pb0 2 = 90
Sodium perborate ........ 0.25 0.0008 Available O 2 = 9
Sodium peroxide, R ...... 0.7 0.0039 Na20, = 90
R. = reagent.
Amount Equiva-
used, lent of Official
Substance Gm. or 1 ce. requitement,
0.1 N per cent
ce.
KMnO.
----------- --- --- --- ----------
U.S.P.
Calcium bromide ............ . 0.4 0.009996 CaBr, = 84 to 94
Calcium gluconate ... ....... . 0.5 0.002804 C"O = 12.4 to 12.8
Calcium lactate ............. . 0.5 0.01091 (CH,CH.OH.COO),Ca = 98
N.F.
Calci urn carbonate, tablets of. 0.6" 0.005004 CaCO, = 92.5 to 107.5'
Calcium gluconate, ampuls of. 0.5a 0.02242 C"H,,014Ca.H,O = 95 to lOS'
Calcium lactate, tablets of .... 1.5· 0.01541 (CH,CH.OH.COO),Ca.5H,0 = 92.5
to 107.5'
Exercise 43
Object.-Assay of Sodium Nitrite.
Materials Required.-1 Gm. of sodium nitrite.
50 cc. of 0.1 N potassium permanganate.
5 cc. of sulfuric acid.
0.1 N oxalic acid.
Procedure.-l. "Dry about 1 Gm. of Sodium Nitrite to constarit weight
over sulfuric acid, weigh accurately in a stoppered weighing-bottle, dis-
solve the salt in a volumetric flask with sufficient distilled water to make
100 cc., and add 10 cc. of this solution, from a pipette, to a mixture of 50 cc.
of tenth-normal potassium permanganate, 100 cc. of distilled water, and 5
cc. of sulfuric acid. When adding the sodium nitrite solution, immerse the
tip of the pipette beneath the surface of the permanganate mixture."
OXIDATION-REDUCTION METHODS 145
Exercise 44
To Determine the Purity of Calcium Carbonate.-Calcium
and lead salts can be assayed volumetrically by precipitation
with standard oxalic acid added in excess and subsequent titra-
tion of the excess acid with standard potassium permanganate
solution.
Object.-Assay of Precipitated Calcium Carbonate.
Materials Required.-About 0.4 Gm. of precipitated calcium carbonate.
10 ce. of diluted hydrochloric acid.
100 cc. of 0.1 N oxalic acid.
Ammonia water, 10 per cent.
Diluted sulfuric acid.
0.1 N potassium permanganate.
Procedure.-l, "Dry about 0.4 Gm. of Precipitated Cal~um Carbonate
to constant weight at 200°C., weigh accurately, dissolve it in a mixture of
10 cc. of diluted hydrochloric acid and 10 cc. of distilled water, and boil the
solution to expel all carbon dioxide."
2. Addition of NH 40H to H 2C 20 4:
H 2C20 4 + 2NH40H~(NH4)2C204 + 2H 20
3. Double decomposition between CaCl 2 and (NH4)2C 20 4:
CaCl 2 + (NH4)2C204~CaC204 + 2NH 4CI
4. Filtrate of (NH 4)2C 20 4 acidulated with H 2S0 4:
(NH4)2C20 4 + H2S04~H2C204 + (NH4)2S0<t.
5. Residual titration of excess H 2C 20 4 with KMn04:
5H 2C20 4 + 2KMn04 + 3H2S04~K2S04 + 2MnS04
+ lOC02 + 8H 0 2
Amount Equiva-
Official
used, lent of 1
Substance requirement,
Gm. cc. 0.1 N
per cent
or cc. H 2C 2O.
U.S.P.
Calcium carbonate, precipitated 0.4 0.005004 CaCO. = 98
Calcium chloride .............. 0.3 0.00555 CaCh = 75 to 85
Calcium chloride, fused, R .. ... 0.3 0.00555 CaCl. = 94
Calcium hydroxide ............. 0.3 0.003705 Ca(OHh = 95
Chalk, prepared ............... 3.5 0.005004 CaCO. = 97
Lead acetate ............. .... . 5 0.01626 Pb(C.H 3 0.). =
85.31 to 89.57
Lead monoxide, R ............. 0.4 <;>.0116 PbO = 98
Lime, R ......... ,."."., .. " 1 0.002804 CaO = 95
N.F.
Calcium chloride, ampuls of ..... O,25 a 0.007351 CaCI..2H 20 = 95
to 105'
Lead monoxide ... , .... , ....... 0,4 0.01116 PbO = 97
Lead subacetate, solution ...... 1 0,01036 Pb = 22.5
Lead subacetate, solution, dilute 50 0.01036 Pb = 0.7 to
O.8W/V
Lime (calcium oxide) ..... , ., ... 1 0.002804 CaO = 95
R. = reagent.
a Amount of ingredient Bought.
b Per cent of the labeled amount.
blue
Exercise 46
Exercise 47
Equiva- Official
Amount
Substance lent of requirement,
used
1 cc. per cent
U.S.P.
Mass of ferrous carbonate ......... 1 Gm. 0.01158 FeCO, = 36 to
41
Pill of ferrous carbonate .......... 3 pills 0.01158 FeCO, = 0.06
Gm. per pill
N.F.
Saccharated ferrous carbonate ...... 2Gm. 0.01158 FeCO, = 15
CHAPTER IX
or
12 + HOH HI + HOI
155
156 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
or
and
HaAsOa + HOI----7H aAs0 + HI
4
or
KI + HCI----7KCI + HI
When a readily reducible substance is present, it reacts with the
hydriodic acid oxidizing the ionic iodine to the molecular state: _
2FeCI s + 2HI~2FeCI2 + 12 + 2HCl
or
2Fe+++ + 2I-~2Fe++ + 12
2 X 3( +) + 2( -) = 2 X 2( +)
OXIDATION AND REDUCTION 157
The ferric chloride is reduced at the expense of the iodine.
Since each mole of Fe+++ oxidizes 1 Gm.-atom of iodine to the
molecular state, the amount of Fe+++ which is reduced in a given
reaction can be determined by titrating the iodine oxidized to the
molecular state with a standard solution of a reducing agent
such as sodium thiosulfate. Since the reducing agent removes
the iodine as fast as it is formed, the reaction proceeds to
completion.
Iodometric methods include some of the most exact processes
of volumetric analysis, because, under proper conditions, the
presence of one part of iodine in several million parts of solution
can be recognized by means of starch indicator solution.
Starch Indicator Solution.-This solution is prepared as
follows:
Triturate 1 Gm. of arrowroot starch with 10 cc. of cold distilled
water in a mortar to form a thin paste. Heat about 200 cc.
of distilled water to boiling, add the starch paste to it with con-
stant stirring. Boil the mixture gently for about 30 min. or
until it forms a thin translucent liquid. Since solution of starch
deteriorates rapidly, it should be prepared freshly each day.
Upon hydrolysis in hot aqueous solution starch forms l1-amy-
lose, the soluble portion, and a-amylose, the insoluble portion.
The blue color of starch solution with iodine is thought to be
due to the formation of a colloidal sol made up of l1-amylose,
iodide ion, iodine, and water. Both iodide ion and iodine must
be present fo~ the production of blue color. The blue color is
discharged in the presence of hydroxyl ion if the latter is present
in high concentration. Consequently, titrations with starch
as indicator should not be made in the presence of alkali hydrox-
ides or carbonates, but cold, dilute solutions of alkali bicarbonate
do not affect the end point appreciably.
Standard Solutions.-The standard solutions employed in the
official assays by iodometric methods are 0.1 N iodine and 0.1 N
sodium thiosulfate.
Exercise 48
Exercise 49
Object.-To Prepare 0.1 N Ionine Solution.
Materials Required.-13 Gm. of pure iodine.
36 Gm. of potassium iodide .•
Procedure.-"Weigh accurately about 12.75 Gm. of reagent iodine and
transfer it quickly into a solution of 36 Gm. of potassium iodide in 100 cc.
of distilled water. After solution is complete, dilute to exactly 1000 cc. at
160 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
25°C. From the weight of the iodine used calculate the normality. The
normality of the solution should frequently be redetermined."
K1 + 12 KIa
In the presence of reducing agents, the reaction proceeds quanti-
tatively to the left, and the solution reacts like a solution of
iodine alone.
The iodine should be weighed accurately in a glass-stoppered
weighing bottle, transferred quantitatively to the solution of
36 Gm. of KI in 100 cc. of distilled water, and after it is com-
pletely dissolved, the soll!tion should be made up to exactly
1,000 cc. The solution of potassium iodide used to dissolve
the iodine is of sufficient concentration to dissolve the iodine
rapidly so that no appreciable loss will occur due to volatilization.
If pure reagent iodine is used in preparing this solution, it will be
approximately tenth-normal and need not be standardized. Due,
however, to the difficulty of weighing exact quantities of iodine,
it is usually more convenient to prepare a solution of app~oximate
strength and standardize it against 0.1 N sodium thiosulfate
solution as directed in the following exercise.
Exercise 50
Object.-To Prepare and Standardize 0.1 N Iodine against
Sodium Thiosulphate.
Materials Required.-14 Gm. of pure iodine.
36 Gm. of potassium iodide.
0.1 N sodium thiosulfate,
Starch test solution.
Procedure.-Dissolve about 14 Gm. of reagent iodine in a solution of
36 Gm. of potassium iodide in about 100 'cc. of distilled water, diluting-
finally to 1,000 cc. Carefully measure from a burette 25 cC. of this solution
into a flask, then add gradually and cautiously from a burette 0.1 N sodium
thiosulfate, shaking constantly, until the color of the solution is but slightly
yellow, then add a few drops of starch T.S. and continue the addition of the
0.1 N sodium thiosulfate until the blue color is just discharged. Note the
number of cubic centimeters of the 0.1 N sodium thiosulfate consumed, and
OXIDATION AND REDUCTION 161
then dilute the iodine solution so that 25 cc. will require for decolorization
exactly 25 cc. of the 0.1 N sodium thiosulfate at standard temperature.
,ICI + KI KCl + 12
The sodium thiosulfate reacts with the iodine to form sodium
iodide and sodium tetrathionate, and a very slight excess of
thiosulfate discharges the blue color of the indicator:
12 + 2Na2S20a 2NaI + Na2S406
If 25 cc. of approximately 0.1 N iodine require exactly 25 cc.
of 0.1 N sodium thiosulfate, the iodine is exactly tenth-normal,
but,' if only 24 cc. of 0.1 N iodine solution are required, the
solution is stronger than normal and each 24 cc. of iodine solu-
tion must be diluted to 25 cc. to secure an exactly 0.1 N solution.
Since 0.1 N iodine solution deteriorates, it will not remain
precisely tenth-normal very long. It is therefore best to calculate
the normality of the solution and employ it as a standard solutIon
of known value. In the above case, the approximately 0.1 N
iodine solution would be 25/24 = 1.0417 times tenth-normal
and should be labeled 0.1042 N iodine. Whenever the solution
is used in a determination, the number of cubic centimeters of
0.1 N iodine employed may be calculated; i.e., cubic centimeters
approximately 0.1 N iodine X 1.0417 = cubic centimeters
0.1 N iodine.
Iodine solutions may also be standardized against pure arsenous
oxide (see Exercise 51).
Questions and Problems
1. Why may iodine containing chloriJ;le or bromine as impurity be used to
prepare standard solutions of iodine when the solution is standardized
against sodium thiosulfate?
2. What is the normality of a solution containing 1.5420 Gm. of iodine
in 100 cc.?
3. If 24.25 cc. of iodine solution requires 25 cc. of 0.0858 N Na 2S20S. what
is the normality of the iodine solution?
162 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Exercise 51
Object.-Assay of Arsenic Trioxide.
Materials Required.-About 0.2 Gm. of arsenic trioxide.
Sodium hydroxide test solution prepared by dissolving 4.3 Gm. of NaOH
in sufficient distilled water to make 100 cc.
Diluted sulfuric acid.
2 Gm. of sodium bicarbonate.
0.1 N iodine.
Starch indicator solution.
Procedure.-l. Dissolve about 0.2 Gm. of arsenic trioxide previously
dried to constant weight at 100°C., and accurately weighed, in 20 cc. of
boiling distilled water, and gradually add sodium hydroxide T.S. until
complete solution results.
Amount
Equiva-
used, Official requirement,
Substance lent of
Gm. or per cent
1 cc.
cc.
---
U.S.P.
Antimony and potassium tartrate .... 0.5 0.01670 K(SbO)C.H.O,.UH,O = 99
Arsenic triiodide ................. 0.5 0.02278 AsI, = 99
Arsenic trioxide ... ....... 0.2 0.004946 As,O, = 99.8
Arsenous acid, solution .............. 20 0.004946 As,O, = 0.975 to 1.025W/V
Potassium arsenite, solution. .... 20 0.004946 As,O, = 0.975 to 1.025W/V
Sodium thiosulfate ..... .... .... 0.5 0.01581 Na,S,O, = 99
Tryparsamide ......... .
. . . . . . . . . . 0.2 0.003746 As = 25.1 to 25.5
N.F.
Arsenic and mercuric iod.ide, solution
(for AsI,) ........................ 25 0.02278 AsIa = 0.95 to 1.05W/V
Sodium cacodylate, ampuls ... ....... 0.2" 0.007998 Na(CH,),AsO, = 69 to 76'
Sodium thioBulfate, ampule ........... I" 0.01581 Na,S,O, = 60.5 to 66.9'
Amount
Equiva-
used, Official requirement,
Slfbstance lent of
Gm. per cent
1 cc.
or cc.
U.S.P.
Iodine ...................... 0.5 0.01269 12 = 99.5
Iodine, compound solution of. 5.0 0.01269 12 = 4.5'to 5.5W IV
Iodine pentoxide, R .......... 0.5 0.002782 1 20. = 99.5
Iodine, tincture of ........... 5.0 0.01269 12 = 6.5 to 7.5W IV
Iodine, tincture of, mild ...... 5.g 0.01269 12 = 1.8 to 2.2W IV
N.F.
~odine, ampuls of. ........... o. 175a 0.01269 12 = 95 to lO5W IVb
Iodine, stronger tincture of ... 2.0 0.01269 12 = 16 to 17WIV
Iodic acid, R ................ 0.1 0.002932 HIO s = 99.8
R. = reagent.
a Amount of ingredient Bought.
b Per cent of the labeled amount.
166 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Amount
Equiva-
used, Official requirement,
Substance lent of
Gm. or per cent
1 cc.
CC.
- ---
U.S.P.
Acetone .................. l.0 0.0009675 CR,COCR, = 99
Mercurous chloride ........ 0.7 0.02361 HgCI = 99.6
Mercurous iodide .......... 1.0 0.03275 HgI = 99
Methylthionine chloride ... 0.12 0.005328 C 16H 1S N 3C1S = 98.5
Sodium bisulfite, R ........ .... 0.005203 NaHSO, = 90
Sodium sulfite, R .......... 0.25 0.006303 Na 2S03 = 95
Sulfurous acid, R .......... 2.0 0.003203 S02 = 6
N.F.
Mercurous chloride, mild,
and sodium bicarbonate,
tablets of ............... 0.3" '" 0.02361 HgCI = 92.5 to 107.5b
Mercurous chloride, mild,
tablets of ............... 0.3" 0.02361 HgCl = 92.5 to 107.5b
R. = reagent .
• Amount of ingredient sought.
, Per cent of the labeled amount.
168 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Exercise 54
Object.______:_Assay of Solution of Ferric Chloride.
Materials Required.-About 2 Gm. of solution of ferric chloride.
5 cc. of hydrochloric acid.
3 Gm. of potassium iodide.
0.1 N sodium thiosulfate.
Starch indicator solution.
Procedure.-l. Transfer about 2 Gm. of a solution of ferric chloride to
a tared flask, stopper, and weigh accurately; add 5 cc. of hydrochloric acid,
25 cc. of distilled water, and about 3 Gm. of potassium iodide. Securely
stopper the flask, and allow the mixture to stand for 5 min.
Amount Equiva-
used, lent of Official requirement.
Substance
Gm. or per cent
1 cc.
cc.
--------- ~---I--- ---1--------
U.S.P.
}'erric
chloride, solution of .. .......... . 2.0 0.005584 Fe = 10 to 11
Ferricchloride, tincture of. ..........-' . 5.0 0.005584 Fe = 4.5
Ferriccitrate, R . ................... . 1 0.005584 Fe = 16.5 to 18.5
Ferricsulfate. solution of ............. . 1.5 0.005584 Fe = 9.5 to 10.5
Iron and ammonium nitrates ..... ... , . 1.0 0.005584 Fe = 16.5 to 18.5
Iron and ammpnium citrates, green . .. . 1 0.005584 Fe = 14.5 to 16
N.F.
Ferric citrochloride. tincture of. .... " 5.0 0.005584 Fe = 4.48 W IV
Ferric glycerophosphate .............. . 0.5 0.005584 Fe = 17
Ferric hypophosphite ................. . 1.0 0.005584 Fe = 21.8
Ferric oxide, saccharated .............. . 8.0 0.005584 Fe = 2.8 to 3.2
Ferric phosphate, soluble . ............ . 1.0 0.005584 Fe = 12 to 15
Ferric pyrophosphate, soluble. . . . . .. 1.0 0.005584 Fe = 10.5 to 12.5
Ferric subsulfate, solution of ......... . 1.0 0.005584 Fe = 20 to 22WIV
Iron. and ammonium acetate, solution of. 25 0.005584 Fe = 0.16 to 0.20W/V
Iron and ammonium citrates, green,
t
R. = reagent.
" Amount of ingredient sought.
b Per cent of the labeled amount.
170 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Exercise 55
Object.-Assay of Chlorinated Lime.
Materials Required.-About 4 Gm. of chlorinated lime.
1 Gm. of potassium iodide.
5 cc. of acetic acid.
0.1 N sodium thiosulfate.
Starch indicator solution.
Procedure.-l. "Transfer to a mortar about 4 Gm. of ChldrinatedLime,
accurately weighed in a tared weighing bottle, using 50 cc; of distilled water.
Triturate thoroughly, and pour the mixture into a 1,000 cc. graduated flask,
rinsing the mortar with distilled water to make 1,000 cc. Stopper the flask
and allow it to stand for ten minutes."
Amount
Equiva-
used, Official requirement,
Substance lent of
Gm. or per cent
1 cc.
cc.
U.S.P.
Chloramine-T .......... 0.2 0.001773 Cl (active) = 11.5 to 13
Dichloramine-T ........ 0.1 0.001773 Cl (active) = 28 to 30
Chlorinated lime, R ..... 4 0.003546 Cl (available) = 30
Sodium hypochlorite,
solution of ........... 5 0.003723 NaOCI = 4 to 6
Sodium hypochlorite,
solution of, diluted ... 25 0.003723 NaOCl = 0.45 to 0.50W IV
R. = reagent.
Exercise 56
Object.-Assay of Cupric Sulfate.
Materials Required.-1 Gm. of cupric sulfate.
4 cc. of acetic acid.
3 Gm. of potassium iodide.
0.1 N sodium thiosulfate.
Starch indicator solution.
Procedure.-"Dissolve about 1 Gm. of Cupric Sulfate, \ accurately
weighed, in 50 cc. of distilled water, add 4 cc. of acetic acid and 3 Gm. of
potassium iodide, and titrate the liberated iodine with tenth-normal sodium
thiosulfate, starch T.S. being used as indicator. Each cubic I centimeter
of tenth-normal sodium thiosulfate is equivalent to 0.01596 Gm. of CUS04."
This assay is based on the reaction between cupric sulfate
and potassium iodide in which the copper is precipitated as
cream-colored cuprous iodide and one atom of iodine is liberated
for each cupric ion present:
2CUS04 + 4KI~Cu212 + 2K2S0 + 12
4
2(159.63)
or
2Cu++ + 4I-~2Cu+ + 21- + 12
Each cubic centimeter of sodium thiosulfate consumed is
126.92 159.63
equivalent to 10 X 1,000 = 0.01269 Gm,. 12 , to 10 X 1,000
63.57
= 0.01596 Gm. CUS04, and to 10 X 1,000 = 0.00636 Gm. Cu.
OXIDATION AND REDUCTION 173
U.S.P. copper sulfate should contain not less than 63 per cent
or more than 66.8 per cent .of CUS04 corresponding to 98.5
per cent of CuS04.5H20. Calculate the per cent Cu, CUS04
and CuS04.5H 20 in the sample assayed.
Exercise 57
Amount
Equiva-
used, Official requirement,
Substance lent of
Gm. or per cent
1 cc.
cc.
--
U.S.P.
Arsphenamine ..... 0.2 0.003746 'As = 30
Neoarsphenamine .. 0.2 0.003746 As = 19 to 22
N.F.
Sodium arsenate,
exsiccated ....... 0.3 0.009295 Na 2HAsO. = 98
Sodium arse'nate,
solution of. ...... 25 0.009295 Na 2HAsO. = 0.975 to 1.025W IV
OXIDATION AND REDUCTION 175
Exercise 68
Object.-Assay of Thyroid.
Materials Required.-1 Gm. of thyroid.
A nickel crucible.
9 Gm. of anhydro-qs potassium carbona,te.
7 Gm. of anhydrous sodium carbonate.
5 Gm. of potassium nitrate.
50 cc. of solution of chlorinated soda.
About 60 cc. of diluted phosphoric acid (1 to 1).
0.1 Gm. of potassium iodide.
0.005 N sodium thiosulfate.
Starch indicator solution.
Procedure.-l. "Thoroughly mix 1 Gm. of Thyroid, finely powdered and
accurately weighed, with 15 Gm. of an intimate mixture of 138 parts by
weight of anhydrous potassium carbonate, 106 parts of anhydrous sodium
carbonate arid 75 parts of powdered potassium nitrate in a nickel crucible
of about 125-cc. capacity, and spread an additional 5 Gm. of this mixture
evenly over the surface. Heat the crucible with the flame of a Bunsen
burner at such a rate as to attain a dull red color in ten minutes, and continue
the heating at the same temperature for an additional ten-minute period.
At the end of this time the carbonaceous material is completely oxidized
and the mixture has just begun to melt around the wall of the crucible.
Cool the fusion mixture and place the crucible and contents in a 400-cc.
beaker. Add 150 cc. of hot distilled water and stir until the contents of the
crucible are completely dissolved."
tion of the organic matter present but that some of it reacts with
KI to form KIO g• After carbonization is complete and the
crucible has cooled, the residue is treated with distilled water
which dissolves the iodide, iodate, carbonates, and nitrite.
2. "Transfer the solution to a 500-cc. Erlenmeyer flask and rinse the
beaker and crucible with four, lO-cc. portions of hot distilled water, adding
the rinsings to the solution in the flask. Cool the solution to 15°C. and
add 50 cc. of freshly prepared chlorinated soda T.S. Cautiously add 60 cc.
of dilute phosphoric acid (made by mixing equal volumes of phosphoric acid
and distilled water), place the flask on a hot plate and boil the solution until
a strip of filter paper, moistened with starch-potassium iodide T.S., does not
become blue when held in the vapor in the mouth of the flask. The final
volume of solution in the flask must be about 175 cc., and distilled water
must be added, if necessary, during the boiling to maintain this volume."
Solution is best effected by treating the residue with successive
portions of warm distilled water. The combined solution is
treated with solution of chlorinated soda which functions as an
oxidizing agent to convert any KI present in the solution into
KIO a. The oxidation with sodium hypochlorite N aOOl is carried
out in solution acidulated with phosphoric acid. The reactions,
although more complex, may be represented 8,s:
2NaOOI + H aPOc--tNa 2HP0 4 + 2HOCI
KI + 3HOOI----tKIO g + 3HOl
HOI + HOOl----tHOH + Ob
Excess phosphoric acid is added to liberate all of the combined
chlorine present in the N aOOl. The solution is boiled to drive
off all free chlorine, since chlorine if present would liberate i9dine
from KI.
3. "Cool the solution to about 25°C. and add 10 cc. of a freshly prepared
aqueous solution of potassium iodide (1 in 100). Titrate the liberated
iodine with two-hundredth-normal sodium thiosulfate, adding 3 cc. of
arrowroot starch T.S. as indicator just before the end of the titration. Con-
duct a blank test with the liIame quantities of the same reagents, omitting
only the Thyroid, and fusing as directed, and subtract the volume of two-
hundredth-normal sodium thiosulfate consumed from that consumed by the
Thyroid. Each cubic centimeter of the corrected volume of two-hundredth-
normal sodium thiosulfate is equivalent to 0.0001058 Gm. of I."
Amount
Nor- Equiva-
used, Official require-
Substance malityof lent of
Gm. or ment, per cent
Na 2S20. 1 cc.
cc.
v
U.S.P.
Calcium iodobehenate .. 0.5 0.1 0.002115 12 = 23.5
Thymol iodide ......... 0.25 0.1 0.002115 12 = 43
Thyroid ............... 1.0 0.005 0.0001058 12 = 0.17 to 0.23
Thyroxin .............. 0.02 0.005 0.0001058 12 = 64
178 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Exercise fi9
Equiva-
Amount lent of
Official requirement,
Substance used, 1 cc. of
per cent
Gm. 0.1 N
Na,S,O.
U.S.P.
Amyl nitrite ............ 3.5 0.01171 C.HuONO = SO
Ethyl nitrite, spirit of .... 10 0.007505 C 2H.ONO = 3.5 to 4.5
Glyceryl trinitratc, spirit
of. .. '................ 25 0.0113 C.H.(ONO,). = 1 to 1.1
TABLE XXVI.-OTHER OFFICIAL SUBSTANCES ASSAYED BY TITRATION OF
THE IODINE LmERATED FROM KI WITH 0.1 N Na,S,O.
Equiva-
Amount
lent of
used, Official requirement,
Substance 1 cc. of
Gm. or per cent
0.1 N
cc.
~
Na,S 2O.
U.S.P.
Chromium trioxide .......... 1 0.003334 CrO, = 95
Cupric sulfate ............... 1 0.01596 CUS04 = 63 to 66.S
Potassium bromate, R ....... 0.3 0.002784 KBrO. = 99.S
R. = reagent.
180 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Equiva-
Amount lent of
Substance used, 1 CC. Official requirement, per cent
grams 0.1 N
bromine
U.S.P.
Phenol .......... '" .. 1.5 0.001568 C6H sOH = 98
Phenol, liquefied ....... 1.5 0.001568 C6H,OH = 88
Phenol ointment ....... 2 0.001568 C.H,OH = 1.8 to 2.2
Resorcinol. ........... 1.5 0.001834 C.H.(OH)2 = 99.5
N.F.
Ammonium hypophos-
phite ............... 0.12 0.002077 NH.PH 20. = 97.5
Calcium hypophosphite 0.12 0.002127 Ca(PH20 2). = 98
Manganese hypophos-
phite ............... 0.12 0.002538 Mn(PH 20 2)..H.O = 97
Potassium hypophos-
phite .. " ........... 0.12 0.002604 KPH20. = 98
Resorcinol, mild paste
of. ................ 1 0.001834 C6H.(OH). = 9.5 to 10.5
Resorcinol, strong paste
of ................. 1 0.001834 C.H.(OH)z = 19 to 21
Sodium hypophosphite 0.12 0.002651 NaPH.O •. H 20 = 98
Sodium salicylate in
caffeine with sodium
salicylate ........... 2 0.002668 C 6H •. OH.COONa = 48 to 52
OXIDATION AND REDUCTION 185
Exercise 63
Amount
Equiva-
used, Molarity Official requirement,
Substance lent of
Om. or of KIO. per cent
1 cc.
cc.
---
U.S.P.
Chiniofon, powder . . ............ 0,3 0.05 0,01269 I = 26.5 to 28.9
Iodophthalein, soluble .......... 0.3 0.05 0.01269 I = 61 to 62
Oil, iodized .................... 0.35 0.05 0.01269 I = 39 to 41
Potassium iodide ............. , . 0.5 0.05 0.01660 KI = 99
Sodium iodide ................. 0.5 0.05 0.01499 NaI = 99
N.F.
Arsenic trioxide, tablets of ....... 0.06- 0.02 0.003956 As,O. = 92.5 to 107.5'
Mercuric iodide, red . ........... 0.2 0.05 0.02272 HgI, - 99
Mercuric iodide, r-ed, tablets of .. 0.13- ",0.02 0.009089 HgI, = 91 to 109'
Mercurous iodide, yellow, tablets
of. •........................ O.la 0.02 0.008734 HgI = 91 to 109'
Potassium iodide, solution of .... 5 0.05 0.01660 KI = 97 to 103W/Y
Potassium iodide, tablets of .... , . O.la 0.02 0.006640 KI = 92.5 to 107.5'
Sodium iodide, ampuls of. ....... 0.5" 0.05 0.01499 NaI = 92 to 105'
GASOMETRIC METHODS
or VI = P 2 = K
V 2 PI
where PI and VI are the pressure and vollfme under one set of
conditions and P 2 and V 2 are the pressure and volume under
another set of conditions, K being their constant product. The
magnitude of K depends upon the quantity of gas measured. If
PI and VI are used to represent the observed pressure and volume
of a gas, respectively, and P 2 is standard pressure (760 mm.),
the volume V 2 which the gas will occupy at P 2 may be calculated;
e.g., if a sample of gas measured at 25°C. and 750 mm. pressure
occupies a volume of 50 cc., what volume will it occupy at 25°C.
190 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
or
where VIand V 2 are the volumes of the gas at the absolute tem-
peratures Tl and T 2• Zero on the absolute temperature scale
corresponds to -273°C. The absolute temperature at which
a given analysis is carried out is therefore found by adding 273
to the laboratory temperature expressed in degrees centigrade.
The above equation then becomes
VI 273 +i 1 and V _ V 2 X 273 + tl
or I
V 2 = 273 + t2 I - 273 t2 +
where tl and t2 represent the respective temperatures in degrees
centigrade; e.g., if a sample of gas measures 50 cc. at 25°C.,
what volume would it occupy at ODC., the pressure remaining
constant? Upon substituting in the above equation, we obtain
.50 273 + 25 _ 50 X 273
and V2 298 = 45.81 cc.
V2 = 273 + 0 -
Exercise 65
Object.-Assay of Carbon Dioxide.
Materials Required.-Carbon dioxide compressed in a metallic cylinder
which is provided with a reducing valve.
A gas burette with leveling tube.
A gas pipette.
About 2 lb. of mercury.
150 cc. of 50 per cent KOH solution.
Procedure.-l. "Place a sufficient quantity of mercury in a 100-cc. gas
burette or nitrometer, provided with a two-way stop-cock and a two-way
outlet, and properly connected with a balancing tube. Connect one of the
intake tubes of the nitrometer with a gas pipette of suitable capacity.
Place in the pipette about 125 cc. of 50 per cent potassium hydroxide solu-
tion. Draw the liquid (free from air bubbles) through the capillary opening,
connection and stop-cock opening in the nitrometer by reducing the pressure
in the nitrometer tube and opening the stop-cock controlling the connection
with the gas pipette. Then close the stop-cock."
Official require-
Substance Absorption reagent
ment, per cent
U.S.P.
Carbon dioxide .. .... Potassium hydroxide CO. = 99
Ethylene ............ Bromine CH. = CH 2 = 99
Nitrogen monoxide .. Water N 20 = 95
Oxygen ............. Copper with NH.CI and 0=99
NH 40H
194 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Exercise 66
Exercise 67
Object.-Assay of Spirit of Ethyl Nitrite.
Materials Required.-1 Lunge nitrometer.
1 10 cc. delivery pipette.
1 100 cc. volumetric flask.
40 cc. of spirit of ethyl nitrite.
0.5 Gm. of potassium bicarbonate.
60 cc. of alcohol.
1.65 Gm. of potassium iodide.
5 cc. of diluted sulfuric acid.
Procedure.-1. Transfer about 40 cc. of spirit of ethyl nitrite, which
has been previously shaken with 0.5 Gm. of powdered potassium bicarbon-
ate, to a tared, 100 cc. measuring flask, and weigh accurately. Add suffi-
cient alcohol to bring the volume to exactly 100 cc. and mix thoroughly.
of the gas will contain 0.0013406 Gm. At 25°C. and 760 mm.
pressure, 1 l. of the gas will contain 1.3406 X 2732~ 25 =
1.2281 Gm., and each cubic centimeter of nitric oxide gas will
contain 0.0012281 Gm. of NO.
The volume of gas being known and the temperature in degrees
centigrade and the barometric pressure in the laboratory having
been ascertained, the weight of nitric oxide gas evolved by a
given weight of spirit of ethyl nitrite may be calculated; e.g., an
aliquot portion of an alcoholic solution of spirit of ethyl nitrite
equivalent to 4.0 Gm. of the spirit when assayed evolved 50 cc.
of nitric oxide measured at 21°C. and 740 mm. pressure. What
percentage by weight of ethyl nitrite did the sample contain?
Substituting in the algebraic equation which expresses the com-
bined laws of Boyle and Charles,
V t = PPlTl
2V 2 T t we obtal'n V = 740 X 50 X 298 = 4935
1 760 X 294 . cc.,
the volume corrected to 25°C. and 760 mm. pressure. 49.35 X
0.0012281 = 0.06061 Gm. NO contained in 49.35 cc., at 25°C.
and 760 mm. pressure. ~
Since 1 mole, 75.05 Gm., of ethyl nitrite, C 2H oN0 2, evolves 1
0,
mole, 30.01 Gm., of nitric oxide, NO, each gram nitric oxide is
the approximate equivalent of 75/30 = 2.5 Gm. ethyl nitrite,
and 0.06061 Gm. of NO is equivalent to 0.06061 X 2.5 = 0.1515
Gm. C 2H oN0 2 •
The percentage by weight of ethyl nitrite contained in the
. 0.1515 X 100
sample IS therefore 4.0 = 3.79 per cent. Calculate
the percentage of ethyl nitrite present in the sample of spirit
assayed.
Conunent.-When a gas is measured above a liquid, the total
pressure observed'is due to the vapor pressure of the liquid plus
the pressure of the gas. In the assay of spirit of ethyl nitrite,
the nitric oxide gas evolved is measured above a solution' mixture
consisting primarily of water and alcohol. According to Dalton's
law, each gas in a mixture of gases exerts the same pressure as it
would if it were present alone. The vapor pressure of water
at 25°C. has been found to be equal to 23.55 mm. of mercury at
DoC., and that of alcohol has been found to be equal to 5.94 mm.
of mercury at O°C. The pressure exerted by the nitric oxide gas
GASOMETRIC METHODS 199
SOLUBILITY
Numerous factors affect the rate and the extent of the solu-
bility of a substance in a given solvent as follows:
1. The solubility of most of the official substances is increased
by a rise in the temperature at which solution is effected. There
are numerous exceptions to this generality, however; e.g., gases,
calcium salts; and ether are less soluble in hot thah in cold water.
Since the solubility of substances varies marketlly with slight
changes in temperature, it is very important that a constant
temperature be accurately maintained throughout a solubility
determination.
2. Substances in a fine state of division dissolve more rapidly
than large crystals or particles because the tot!)'l surface area
exposed to the action lof the solvent
is much greater when. the substance
is powdered.
3. The purity of the ~ubstance and
of the solvent must be assured in all
solubility determinations, since slight
amounts of impurity in either may
cause considerable- variation in the
results. In the official state~ents of
solubility, it is assumed that both the
substance and the solvent employed
conform to the official tests for purity.
4. The position of the solute in the
solvent affects the rate of solution.
If the solute is allowed to lie on, the
FIG. IS.-Apparatus for sol-
ubility determinations. A As- bottom of the vessel, it becomes
sembled apparatus. B Stirrer. surrounded by a layer of concentrated
solution which prevents the access of fresh portions of the solvent
to the surface of the solute.
The determination of the solubility of a solid in a liquid neces-
sitates the preparation of a saturated solution. The prod.uction
of a saturated solution of this type may be carried out in the
apparatus illustrated in Fig. 18. This apparatus consists of a
hard-glass test tube A of medium size into wh~ch the solvent and
solute are placed and stirred vigorously by means of a motor-
driven glass screw stirrer B. The stem of the stirrer passes
through a glass tube, inserted through a well-cleaned stopper by
SOLUBILITY 205
and determine the amount of boric acid contained in it in the same manner
as before.
ments in the set of four are calibrated to read from 0.600 to 1.000,
from 1.000 to 1.400, from 1.400 to 1.800, and from 1.800 to 2.200.
When making a specific gravity determination with a hydrom-
eter, the thoroughly cleaned instrument should be allowed to
sink in the liquid gradually until it is at rest, then depressed
about 1 in. to 'moisten a portion of the stem, allowed to come to
equilibrium, and the reading taken.
Exercise 71
Object.-To Prepare 200 cc. of Sulfuric Acid Containing
10 Gm. of H 2 S0 4 per 100 cc.
Materials Required.-20 cc. of concentrated H 2S0 4 •
A hydrometer calibrated from specific gravity 1:000 to 1.400 at 25°0.
Procedure.-Dilute 20 cc. of pure concentrated sulfuric acid to 100 cc.
with distilled water, allow the resulting solution to acquire a temperature
of 25°0., and take its specific gravity as accurately as possible with the
hydrometer.
Exercise 73
Since the camphor is lighter than water, the weight of the sinker
and camphor is less than the weight of the sinker alone. The
difference between the weight of the sinker and camphor in water
and the weight of the sinker alone in water plus the weight of the
camphor in air is a measure of the water displaced by the camphor
and also a measure of its buoyant power, e.g.:
Exercis.e 74
• Specific Specific
Substance gravity, Substance gravity.
25°C. 25°C.
U.S.P. U.S.P.
Acid, aeatic, glacial. ...... 1.047 to 1.050 dwarf pine needles ...... 0.853 to 0.869
Alcohol (at 15.56°C.). , . (n.m.t.) 0.816 eucalyptus ............. 0.905 to 0.925
Al c oh 01, d eh yd r a ted !en~el. ................ 0.953 to 0.973
(15.56°C.) .............. (n.m.t.) 0.798 Jumper ................ 0.854 to 0.879
Alcohol, diluted (15.56°C.). 0.935 to 0.937 lavender ............. 0.875 to 0.888
Amyl nitrite............ 0 865 to 0.875 lemon ................. 0.849 to 0.855
Balsam, Peruvian ......... 1.150 to 1.170 mustard ............... 1.013 to 1.020
Benzin, petroleum, purified 0.634 to 0.660 myristica .............. 0.859 to 0.924
Brandy .................. 0.933 to 0.921 orange .. : .............. 0.842 to 0.846
Bromine, R.1 ............. (n.l.t.) 3.099 peppermmt ............ 0.896 to 0.908
Camphor, spirit of ........ 0.824 to 0.826 rose' ......•........... 0.848 to 0.863
Carbon tetrachloride ...... 1.588 to 1.590 rosemary .............. 0.894 to 0.912
Chloroform .............. 1.474 to 1.478 santa!....... ........ 0.965 to 0.980
Collodion ................ 0.765 to 0.775 sassafr'!s. . . . .. ........ 1. 065 to 1.077
Copaiba ................. 0.930 to O. 995 spearmmt .. '" ........ 0.917 to 0.934
Creosote ................. (n.l.t.) 1.076 tar, rectified ............ 0.960 to 0.990
Creosote carbonate ........ (n.l.t.) 1.145 turpentine ............. 0.854 to 0.868
Cresol. . . . . . . . . . . . . . . . . .. 1.030 to 1 .038 turpentine, rectified.. .. 0.853 to 0.862
Ether ................... 0.713toO.716 Oleoresin of aspidium ...... (n.l.t.) 1.0
Ether, absolute, R ........ (n.m.t.) 0.710 Ox bile .................. 1.015 to 1.025
Ethyl acetate, R .......... 0.893 to 0.898 Paraffin, chlorinated ....... 1.00 to 1.07
Ethyl nitrite. spirit of. .... (n.m.t.) 0.823 Petroleum' ............... 0.820 to 0.865
Ethyl oxide .............. 0.713 to 0.716 Pet~olatum,liquid ........ 0.828 to 0.905
Eucalyptol. .............. 0.921 to 0.923 Rosm................... 1.07 to 1 09
Eugenol. . . . . . . . . . . . . . . .. 1.066 to 1.070 Spermaceti ............... 0.938 to 0: 944
Ferric chloride, solution of 1. 29 to 1. 32 Sodium hypochlorite, di-
Glycerin ................. (n.l.t.) 1.249 luted solution of ........ (n.Lt.) 1.205
Giyceryl trinitrate, spirit of 0.814 to 0.820 Tar, juniper .............. 0.950 to 1.055
Honey' .................. (n.Lt.) 1.099 Terebene ................ 0.860 to 0 865
Malt, extract of. ......... 1.350 to 1.430 Wax, white and yellow .... 0.950 to 0:960
Methyl salicylate (natural) 1.176 to 1.182 Whisky .................. 0.935 to 0.923
Methyl salicylate (synthet- N.F.
ic) .................... 1. 180 to 1.185 Anethol. ... : .............. 0.983 to 0.987
Oil (fixed) of Ether, spmt of ........... 0.784 to 0.794
almond, expressed ....... 0.910 to 0.915 Ethyl acetate ............. 0.892 to 0.898
castor ................. 0.945 to 0.965 Caramel................. (n.l.t.) 1.35
chaulmoogra ........... 0.940 to 0~960 Hamamelis water... 0.979 to 0.982
cod liver ............... 0.918 to 0.927 Oil (fixed) of
corn ................... 0.914 to 0.921 croton ............... 0.935 to 0.950
cottonseed ............. 0.915toO.921 sesame ................ 0.916toO.921
linseed ................. 0.925 to 0.935 Oil (volatile) of
olive ....... \ .......... 0.910 to 0.915 birch tar. rectified .... '" 0.886 to 0.950
theobroma' ............ 0.858 to 0.864 bitter orange ........... 0.845 to 0.851
Oil (volatile) of caraway ............... 0.900 to 0.910
anise .................. 0.978 to 0.988 cardamom . . . . . . . . . . . 0.917 to 0.947
bitter almond. . . . . . . . .. 1. 038 to 1. 060 myrcia ................ 0.962 to 0.990
chenopodium ........... (n.l.t.) 0.950 orange flowers .......... 0.863 to 0.880
cinnamon .............. 1.045 to 1.063 pimenta........ .... 1.018 to 1.048
clove .................. 1.038 to 1.060 thyme ................. 0.894 to 0.930
coriander .............. 0.863 to 0.875 Tetrachlorethylene . . . . . . 1.600 to 1.610
(n. m. t.) = not more than. (n. I. t.) = not less than. R. = reagent.
1 Saturated with water.
, Diluted with 2 times its volume of distilled water.
, At 100°C. compared to water at 25°C.
'At 30°C.' compared with water at 15°C .
• At 60°C.
CHAPTER XIII
10 cm. long; (2) a stirring rod bent into a circle at one end to fit
the above tube and at an angle at the other end to permit easy
manipulation; (3) a standard th~rmometer covering the desired
range of temperature; (4) an auxiliary thermometer to take the
emergent stem correction, preferably graduated from 20 to
100°C.; (5) a capillary glass tube about 6 cm. long and 1.0 mm.
in diameter sealed at one end.
For temperatures up to 200°C., a purified, concentrated sulfuric
acid is a suitable bath. For higher temperatures, up to about
350°C., a pure grade of cottonseed oil (almost colorless) will
serve for a limited number of determinations. Other, though
less desirable, substitutes for sulfuric acid for use at high temper-
atures are: (1) a pure grade of paraffin which has been freshly
distilled; (2) clean, white, hydrogenated cottonseed oil. A very
satisfactory bath is prepared by cautiously boiling toge~her, for
from five to ten minutes under a hood, a mixture of 70 parts of
sulfuric acid and 30 parts of potassium sulfate, stirring constantly
until the potassium sulfate is completely dissolved.
The following exercise illustrates the methods used to deter-
mine the melting points of official substances:
Exercise 76
3. Introduce enough of the finely powdered dry salicylic acid into thc
capillary tube to form a column about 0.3 cm. in length.
The salicylic acid may be packed into the sealed end of the
tube by tapping the open end of it into a little mound of the pow-
der, then inverting the tube and tapping it gently on a solid
surface, or by drawing the broad side of a triangular file across
the surface of the tube just below the powder.
4. Attach the charged capillary tube to the thermometer by wetting
both with the acid of the bath, and the tube will then be held in position by
capillary attraction, or attach the capillary tube by means of a rubber band,
clipped from a piece of rubber tubing, in such a position that the column of
salicylic acid is centrally located by the side of the thermometer bulb.
Attach the auxiliary thermometer so that the center of its bulb is as close as
possible to the stem of the main thermometer at a point midway between
the surface of the bath and the 160° graduation mark. Heat the acid bath
by means of a free Bunsen flame until a temperature of about 140°C. is
reached, then carefully regulate the rise in temperature to about 3° per
minute until the substance begins to melt, and then regulate the rise in
temperature to about 0.5° per minute until the salicylic acid is completely
melted, while stirring the bath continually. Record the melting interval
temperature and the temperature registered on the auxiliary thermometer
at the end of the melting.
The temperature at which the column of salicylic acid is
observed to collapse definitely in the capillary tub'e is considered
as the beginning of the melting, the temperature at which the
salicylic acid becomes liquid throughout is considered as the
end of the melting, and the interval between the temperatures
at which the melting begins and ends is taken as the temperature
range of the melting point of salicylic acid.
The rate of rise in the temperature of the bath can be regulated
easily if .the burner is held in the hand so that more or less heat
can be applied as required. Since heat from the burner may
affect the temperature registered on the auxiliary thermometer,
it is advisable to construct a movable platform of stiff paper
around the main thermometer and adjust it to a position just
below the bulb of the auxiliary thermometer.
The temperature observed on the auxiliary thermometer is
used to correct for the contraction of the thread of mercury above
the bath by the following formula:
Correction = 0.00015 X N(T - t) where N represents the
number of degrees from the surface of the bath to the melting
MELTING, CONGEALING, AND BOILING POINTS 229
Melting Melting
Substance point. Substance point,
°C. °C.
(a.) R about. (n.Lt.) = not le8s than. (d.) = with decomposition. R. ~ reagent .
.. Special method. s = sublimes.
MELTING, CONGEALING, AND BOILING POINTS 231
Exercise 76
·Object.-Determination of the Solidification Temperature of
the Fatty Acids of Cottonseed Oil.
Materials Required.-50 cc. of cottonseed oil.
25 Gm. of potassium hydroxide.
100 cc. of glycerin.
15 cc. of alcohol.
"A standard thermometer meeting the following specifications: The
thermometer must have a zero mark, graduations of 0.1 °0. between 10 and
60°C., and auxiliary reservoirs at the upper end and between the 0 and 10°
marks. The cavity of the capillary tube between the 0 and 10° marks must
be at least 1 cm. below the 10° mark, which must be from 3 to 4 cm. above
232 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
the bulb, the total length of the thermometer being about 38 cm. The bulb
should be about 3 cm. long and 6 mm. in diameter, the scale should be
etched on, and the graduations clear-cut and distinct. The thermometer
should be made of the best thermometric glass and thoroughly annealed, so
that scale errors will not increase after continued heating."
Procedure.-l. "Heat 75 cc. of glycerin-potassium hydroxide solution
(made by dissolving 25 Gm. of potassium hydroxide in 100 cc. of glycerin)
to 150°C. in an 800-cc. beaker and add 50 cc. of the clarified fat, melted if
necessary. Heat the mixture for fifteen minutes with frequent stirring, but
do not allow the temperature to rise above 150°0. When saponification is
complete, the mixture is homogeneous, with no particles clinging to the
beaker at the meniscus."
Exercise 77
Object.-To Determine the Boiling Point of Carbon Tetra-
chloride.
Materials Required.-25 cc. of carbon tetrachloride.
A distillation apparatus as illustrated.
Procedure.-Place the asbestos" board on a tripod or other suitable
support. Introduce into the distilling bulb 25 cc. of the liquid to be tested,
insert the thermometer, stand the bulb in an upright position in the per-
foration of the asbestos board, and connect it with the condenser. Then
distil the liquid at the rate of 1 cc. for each 15 to 20 sec., noting the tempera-
ture as Boon as 5 drops of the liquid have distilled into the receiver and when
the last liquid evaporates from the bottom of the flask or when the specified
percentage has distilled over. Correct the reading for any variation in the
236 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
barometric pressure from the normal (760 mm.) by allowing O.l°C. for each
2.7 mm., adding if the pressure is lower, and subtracting if higher than
760 mm.
60
116.9 + 0.le 2-; 733) = 117.9. The boiling point of the acid
should then be reported as b.p'133 = 117.5 to 117.9°C. cor., the
subscript 733 indicating the barometric pressure at which the
determination was made, and the abbreviation" cor." indicating
that the boiling point as reported has been corrected to standard
pressure. If a long-stemmed thermometer is used in the deter-
mination, a further correction for the emergent stem must be
made, as explained under Melting Point, page 229.
A second method is given in the Pharmacopoeia for use with
Jiquids for which the permissible range in boiling temperature
exceeds 5°C. The following is a description of the apparatus
required and the procedure to be followed:
A 200 cc. distilling bulb with an outlet tube at approximately
the center of the neck, forming an angle of from 70 to 75 deg.,
with the lower end of the neck. The length of the neck is from
MELTING, CONGEALING, AND BOILING POINTS 237
REFRACTOMETRIC MEASUREMENTS
The index of refraction is a physical constant frequently made
use of i.n the determination of the identity and purity of drug and
food products. In many cases, it may be used to determine
quantitatively the strength and purity of solutions or the propor-
tions in which liquids are mixed; e.g., the percentage of sugar in
syrup can be estimated directly from the refractivity of the solu-
tion, and the percentage of alcohol in water can also be aetermined
in this way. Although the refractive index is a constant charac-
teristic of many substances such as fats, fatty
oils, waxes, sugars, organic solvents, etc., it is
[ applied almost exclusively in the official stand-
ards as a criterion of the purity of volatile oils.
Index of Refraction.- When a raJ;" of mono-
chromatic light passes from one transparent
substance into another of different optical
density, it is deflected or refracted except
FIG. 28.-Refrac- when it enters perpendicularly to the surface
tion of light.
of con t act between the substances. The
extent and direction of the deflection are dependent upon the
difference between the densities of the two substances. The
angle between the ray in the first medium and a perpendicular to
the dividing surface is termed the angle of incidence i, and the
corresponding angle in the second medium is called the angle of
refraction r. The sin of i and the sin of r are directly proportional
to the velocities of light in the two media. The ratio sin i/sin r
is termed the index of refraction. Thus, the velocities of light
in air and in water are in the ratio of about 4 to 3. The index of
refraction of water with respect to air is therefore about 1.333.
In Fig. 28, I is the less dense medium and II the more dense
medium. A ray of light passing obliquely from I to II will be
deflected so that the angle of refraction r will be less than the
240
itEFRACTOME'l'RIC MEASUREMENTS 241
Exercise 78
The refractiye index of the test plate is etched upon it, and the
reading of th~instrument should correspond to that given on this
plate. If thtJ instrument is not in adjustment, a correction should
be applied to the readings obtained.
2. Remo'l{e the test plate, clean the upper prism with cotton saturated
with alcohol, clamp the prisms together loosely, introduce 2 or 3 drops of
the volatilll oil into the groove at the side of the prisms, and clamp the
prisms together firmly. Adjust the mirror K so that the light is reflected
upon the lower prism, and rotate the alidade until the border line between
the lightl and dark halves of the field of view exactly coincides with the
cross-hai,'rs of the telescope, rotating the compensator prisms to obtain a
sharp uncolored border line if necessary. Read the refractive index of
the oil directly from the graduated sector scale to the fourth decimal place.
Move the aJidade and again determine the refractive index until three
readings are obtained, taking the mean of the readings as the refractive
index of the oiL Note the temperature at which the refractive index is read.
3. A range is given for the refractive index of most of the official volatile
oils. Why?
4. How do variations in temperature affect the inqices of refraction of
liquids?
6. Would you expect that oil of orange would have a greater or smaller
index of refraction at 25 than at 20°C.? Why?
I
TABLE XXXIV.-OFFICIAL SUBSTANCES WITH RE~UlRED REFRACTIVE
INDICES
Temperature,
Substance Official requirement
°C.
U.S.P.
Eucalyptol. ...................... 20 1.455 to 1.460
Oil of anise ....................... 20 1. 5530 to 1. 5600
Oil of bitter almond ............... 20 ~.5428·to 1.5439
Oil of chenopodium ............... 20 1. 4723 to 1. 4790
Oil of cinnamon ................... 20 1 .'6020 to 1. 6135
Oil of clove ....................... 20 1. 5300 to l. 5350
Oil of coriander ................... 20 1.4620 to 1. 4720
Oi~ of dwarf pine needles ........... 20 1. 4580 to 1. 4700
Oil of eucalyptus .................. 20 1 . 4600 to 1. 4690
Oil of fennel. ..................... 20 1 . 5280 to 1. 5380
Oil of juniper ..................... 20 1. 4780 to 1. 4840
Oil of lavender .................... 20 1. 4590 to 1. 4700
Oil of lemon ...................... 20 1.4742 to 1.4755
Oil of mustard, volatile ............ 20 1 . 5268 td 1. 5280
Oil of myristica ......... ......... 20 1. 4740 to'!. 4880
Oil of orange ..................... 20 l.4723 to'1.4737
Oil of peppermint ................. 20 l. 4600 to'!. 4710
Oil of rose ........................ 30 1.457 toh.463
Oil of rosemary ................... 20 1. 4640 to b. .4760
Oil of santal. ..................... 20 1.5000 to 1.5100
Oil of sassafras ................... 20 1 . 5250 to 1. 5350
Oil of spearmint .................. 20 1. 4820 to 1'.4900
Oil of theobroma .................. 40 1 . 4537 to 1. 4578
Oil of turpentine ..... , ............ 20 1. 4680 to 1. ~ 780
N.F.
Anethol. ......................... 25 1. 5580 to 1. 5~10
Oil of caraway .................... 20 1.484 to 1.488
CHAPTER XV
ROTATORY POWER
Many organic substances, such as certain constituents of the
volatile oils, alkaloids, and sugars, possess the power of rotating
the plane of polarized light when the latter is passed through
solutions containing them. Substances which possess this power
are said to be optically active and are designated as dextrorota-
tory when the direction of the rotation is toward the right and as
laevorotatory when it is toward the left.
The optical activity of many substances is a function of their
chemical constitution as well as of their concentration. Con-
sequently, a determination of the rotatory power or lack of
rotatory power of a substance may serve as a means of establish-
ing both its identity and its purity. In some cases, the me as-
u~ement of the optical activity of a substance may also give
some indication of its therapeutic value; e.g., the laevorotatory
alkaloid hyoscyamine is much more active as a mydriatic than
its optically inac.tive isomer atropine.
In a ray of ordinary light, the vibrations are transverse, i.e.,
they take place in a. plane at right angles to the direction of
propagation, but the vibration direction is constantly changing.
In a ray of plane-polarized light, commonly termed polarized light,
the vibrations are also transverse, but they take place in only
one direction.
The polariscope and the polarizing microscope are used in the
determination of the optical activities of liquid and solid sub-
stances, the polarizing microscope being employed more often
for the examination of solid SUbstances, while the polariscope
is used primarily for the examination of liquids.
When a ray of ordinary light is passed through a specially
constructed prism made of Iceland spar, such as the Nicol's
prism, the emergent light wave vibrations take place in one
plane, and the light is' said to be plane-polarized. If another
247
248 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
or [alb = l~a
For calculating the specific rotation [k] using these formulas,
the determination of the following factors is necessary:
a = observed rotation in degrees of the liquid at temperature
t using a sodium light.
1 = the length of the tube in decimeters.
250 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
ClW
FIG. 34.-Diagram of the optical parts of a polarimeter.
Exercise 79
pare the specific rotation of the sample examined with th~ official
requirement.
Questions and Problems
1. What is polarized light? How can it be obtained?
2. Show diagrammatically the essential parts of the polariscope used
and explain the function of each part.
3. What factors influence the rotatory power of a substance?
4. Define the term specific rotatory power.
TABLE XXXV.-OFFICIAL SUBSTANCES WITH REQUIRED ANGULAR ROTATION
Official Requirement
Substance a= Angular rotation
U.S.P.
Copaiba, volatile oil from .... a = not less than _7 0
Methyl salicylate from gaul-
theria .................... a = not more than -1.5 0
Oil of anise ................. a = +1 to _20
Oil of bitter almond. . . .. . .. a = inactive to +0 0 10'
Oil of cinnamon. . . . . . . . . .. . a = +1 to _1 0
Oil of clove. . . . . . . . . . . . . a = not more than _10 10'
Oil of coriander. . . . . . . . . . .. a = +8 to + 15°
Oil of fennel. ............... a = +12 to +24 0
Oil of juniper. . . . . . . . . . . . . .. a = 0 to -15..0
Oil of lavender .............. a = -3 to -10 0
Oil of lemon. . . . . . . . . . . . . .. a = +57 to +65.6 0
Oil of dwarf pine needles ..... a = -5 to _120
Oil of myristic a . . . . . . . . . . . .. a = + 10 to +30 0
Oil of orange .... ,. . . .. . .... a = +94 to +99 0
Oil of peppermint ........... a -23 to -32 0
Oil of rose .................. a = 1 to 40
Oil of rosemary ............. a = 5 to +10 0
Oil of santal. ............... a = -15 to -20 0
Oil of sassafras .............. a = +2 to +4 0
Oil of spearmint ............. a = -48 to -59 0
Terebene. . . . . . . . . . . . . . . . . .. a = not more than +0.3 0
N.F.
Anethol. . . . . . ... . . . . . . . . . . .. a = 0 to +0.08 0
Oil of bergamot ............. a = +8 to +240
Oil of bitter orange. . . . . . . . .. a = +88 to +980
Oil of caraway .............. a = +70 to +80 0
Oil of cardamom ............ a = +22 to +440
Oil of myrcia ................ a = not more than _3 0
Oil of orange flowers. . . . . . . .. a = + 10 3~' to +9 0 8'
Oil of pimenta .............. a = 0° to _4°
Oil of thyme .... , ........... a = not more than 4 0
Salicin. . . . . . . . . . . . . . . . . . . .. a = 62 to 67 0
ROTATORY POWER 255
5. Explain what the following terms mean: (1) [aut = +4.210; (2)
[aUf = -10°; (3) dextrorotatory; (4) optically inactive.
6. The optical rotation of a sample of oil of chenopodium determined in a
100 mm. tube and having a density of 0.9750 is found to be -12.25 deg.
at 21°. Calculate the specific rotation of the oil.
7. A sblution containing 10 Gm. of sugar in 100 cc. was found to exhibit
an angular rotation of +11.5 deg. when determined in a 100 mm. observa-
tion tube. Calculate the specific rotation of the sucrose.
Concen-
Solvent
Substance
used
trationin [alD = specific rotation
.100 cc.
U.S.P.
Camphor" natural Alcohol 10 Gm. [aut = +41 to +42°
Dextrose ......... Water 10 Gm. [aUf = +52.5 to +53
Ephedrine hydro-
chloride ........ Water 5Gm. [aut = -33 to -35.5°
Ephedrine sulfate .. Water 5Gm. [aut = -29.5 to -32 0
Epinephrine ...... 0.5 N HCI 5 Gm. [aut = -50 to -53.5
Oil, chaulmoogra .. Chloroform 10 Gm. [alit = +48 to +60
Ethyl chaulmoo-
grate ........... Chloroform 50 cc. [a]i,s° = not less than +44.5°
Lactose ........... Water 10 Om. [aUf = +52.2 to +52.5°
Scopolamine hy-
drobromide ..... Water 5Gm. [aut = -22 to -25.75°
Sucrose .......... Water 26 Gm. [alt"O = not less than +65.9°
N.F.
Ephedrine sulfate,
solution of ...... Water 3 Gm. [a11&0 = -28 to -30
256 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
VISCOSITY MEASUREMENTS
The viscosity of a fluid substance is constant for any given
temperature and is a measurable characteristic of the substance.
It is used chiefly as an index of the composition and lubri-
cating value of oils. The viscosities of solutions and liquid
mixtures often vary with their concentration and composition,
however, this property may be used, in many cases, as a rapid
means of analysis. The U.S.P. utilizes the viscosity as a means
of standardizing liquid petrolatum which is employed therapeu-
tically as an intestinal lubricant.
In the U.S.P., viscosity is defined as "a term used to denote
the relative degree of fluidity of a liquid." This definition is
confusing, since fluidity is the reciprocal of viscosity; i.e., fluidity
= l/viscosity. Fluidity may be regarded as a measure of the
tendency of a liquid to flow, whereas viscosity is a measure of the
resistance which a liquid exerts against the tendency to flow.
Viscosity may be defined as the force of friction which tends
to retard movement in a fluid body. The unit of absolute viscosity
is defined as the tangential force required to move a unit area of
plane surface within the liquid with unit velocity relative to another
parallel unit area of plane surface one unit distant from the former
surface, where the unit of force is the dyne (the force necessary
to produce an acceleration of 1 cm. per second per second on a mass
of 1 Gm.), the unit of velocity is the centimeter per second, the unit
of area is the square centimeter, and the unit of distance is the centi-
meter. This unit of absolute viscosity is known as the poise and
it is generally expressed as dyne-second per square centimeter.
The poise is a relatively large unit, and the one-hundredth part
of ~he poise, or a centipoise, is commonly employed as the unit of
absolute viscosity.
Instead of giving results in terms of absolute viscosity, most
methods of determination give the relative viscosity; i.e., the
257
258 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Exercise 83
Object.-Assay of Crocus for Color.
Materials Requlred.-{).l Gm. crocus in fine powder.
266 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Exercise 84
Exercise 85
Object.-To Determine the Amount of Oil of Peppermint in
Spirit of Peppermint.
Materials Required:-5 cc. of spirit of peppermint.
1 cc. of oil of peppermint.
Diluted hydrochloric acid.
Alcohol, 95 per cent (redistilled).
Procedure.-Dissolve 1 cc. of oil of peppermint, accurately measured
from a pipette, in sufficient 95 per cent alcohol to make exactly 10 cc.
Dilute 5 cc. of this solution with 25 cc. of diluted hydrochloric acid, shake
thoroughly, and compare by means of a nephelometer the turbidity pro-
duced with that of an equal volume of spirit of peppermint diluted in the
same manner.
distilled water and 2 cc. of nitric acid, then diluted with distilled
water to 50 ce.
II Sulfate.-The specified quantity of the substance to be tested
BOH B+ + OH-
272
DETERMINATION OF HYDROGEN ION CONCENTRATION 273
For the purpose of this discussion, salts, certain acids, and the
hydroxides of the alkali metals are assumed to be completely
dissociated in dilute aqueous sE>lution.
At equilibrium the ordinary mass action equation will hold as a
first approximation for weak acids
[H+][A-] = Ka
(1)
[HA]
[A-] Ka
[HA] = [H+]' (2)
TABLE XXXVII
Normality, Normality,
pH
hydrogen ions hydroxyl ions
0 1 10-14
1 10-1 10-13
2 10-2 10-12
3 10-3 10- 11
4 10-< 10- 10
5 10-' 10-·
6 10-· 10-8
Neutral potnt 7 10- 7 10-7
8 10-s 10-·
9 10-' 10-'
10 10-1 • 10-4
11 10-11 10-3
12 10- 12 10- 2
13 10- 13 10- 1
14 10-14 1
TABLE XXXVIII
[H+] pH
Times Increased or Decreased CorrespondIng Change
10 COO
5 0.70
2 O.~O
1.5 0.18
1.1 0.04
1.05 0.02
1.023 0.01
E = RT In (H+)'yPH2 +E (5)
F (H+)yP'H2 L,
~ 1
E = 0.0581 log (H+) (7)
Potential at
Calomel eleotrode .
20°C. 25°C. 30°C.
I I
0.1 N KCl. ................... 0.3379 0.3376 0.3371
NKCl. ...................... 0.2860 0.2848 0.2835
Saturated KCl. ............... 0.2496 0.2458 0.2420
o ABC'~ ( (
\ \\
Z
\\1\ Curve A ~Wifh Saturated
KCl Calomel Electrode
Curve 8-Wifh Normal KCl
\~\ Calomel Electrode
3 Curve C-WithTenthNormaJ
4 ~ \\ Calomel Electrode
5
\\\
6 '\ \\
pH
7
1\\\
\ l\\
8
9 .~ l\
~\\
10
1 "\ \\
12 \\\
\ l\\
13
14-
\) l\
0.2 0.3 0.4 0.5 0.9 0.1 0.8 0.9 1.0 1.1 1.2
Voltage
FIG. 43.-Graph showing relation of pH and voltage measured with hydrogen
and calomel electrodes.
5~
6~
<
7~
9~
IO~
II;
IZ~
13:
14'
FIG. 44.-Charaotcristic titration curves. Vertioal scale shows pH values.
690.5; 31 cc. = 860.1; 35.0 cc. = 949.5; 40 cc. = 965.9; 45 cc. = 982.2;
50 cc. = 992.1. Plot the millivolts of electrode potential as ordinates and
the cubic centimeters of NaOH as abscissae. Determine the pH value at
the end point from the curve and calculate the normality of the sodium
hydroxiae solution.
Exercise 88
'Object.-To Determine the End Point of Titration of Acetic
Acid with Sodium Hydroxide Potentiometrically.
Materials Required.-The same as in Exercise 87, except that the 0.1
N hydrochloric acid is replaced by a solution of acetic acid of unknown
concentration.
Procedure.-Proceed as in Exercise 87.
Quinone + 2H + 2( - ) hydroquinQne
0.453 - V
0.0591 = I
og I
H+ = PH were
h V'IS th e measure d vo1tage.
DETERMINATION OF HYDROGEN ION CONCENTRATION 289
4
\
pH
5 \
6
\
1
\
\
8
9 \
10 \
-0.5 -0.4 - 0.. - 0.2- 0.1 0 .. 0.1 .. O.l.
Voltage
FIG. 45.-Graph showing the relation of pH to voltage measured with the
quinhydrone and calomel electrodes at 25°C.
Exercise 90
Molec-
Indicator pH range uJar Color change Solvent
weight
--
Methyl yellow .......... .... 2.9 to 4.0 225 Red-yellow Alcohol
Bromphenol blue ........ ... 3.0 to 4.6 669 Yellow-blue 3.0 cc. 0.05 N NaOH
Methyl red ............... .4.2 to 6.3 269 Red-yellow 7.4 cc. 0.05 N NaOH
Bromcresol purple ........... 5.2 to 6.8 540 Yellow-purple 3.7 cc. 0.05 N NaOH
Bromthymol blue ........... 6.0 to 7.6 624 Yellow-blue 3.2 cc~ 0.05 N NaOH
Phenol red .............. .. 6.8 to 8.4 354 Yellow-red 5.7 cc. 0.05 N NaOH
Thymol blue .. ............ 8.0 to 9.6 466 Yellow-blue 4.3 cc. 0.05 N NaOH
Thymolphthalein ..... , . .... 9.3 to 10.5 430 Colorless-blue Alcobol
~
HCI-KCI Mixtures
Phthalate-Hel Mixture•
Phthalate-NaOH Mixtures
0.5 cc. of the indicator solution to each of them, and then sealing
the tubes. Thus in preparing color standards for phenol red
10 cc. of nine buffer mixtures having pH values of 6.8, 7.0, 7.2,
7.4, 7.6, 7.8, 8.0, 8.2, and 8.4, respectively, are placed in separate
tubes, 0.5 cc. of 0.02 per cent phenol req. indicator solution is
added to each tube, and the tubes are sealed. Each tube is
then labeled with the respective pH value corresponding to
that of the buffer solution which it contains. The tube marked
pH 6.8 will exhibit the yellow color and that marked pH 8.4 will
exhibit the red color of phenol
red, and the tubes with inter-
mediate pH values will show
gradations of color between
yellow and red.
Reliable color standards
covering the pH range 1.2 to
10.4 for all of the required
indicators, guaranteed for one
year, can be purchased. It is
unnecessary to secure color
standards for all of the indi-
cat ors cove ring the range
FIG. 48.-Block comparator.
pH = 1.2 to 10.4 unless deter-
minations of pH on a variety of products of widely divergent
hydrogen ion concentration are to be made. Thus if a solution
has a pH falling between 6 and 8.4, color standards for brom-
thymol blue and cresol red are all that is necessary.
Color Comparators.-Some type of color comparator must be
used to match the color of the unknown with the color standards.
This is especially true if the sample under examination is at all
turbid or colored. Of the numerous devices available, the
LaMotte block comparator (Fig. 48) is 1>est suited for use with
the equipment herein described. This comparator consists of
anyone set of color standards such as bromthymol blue; four
test tubes graduated at 10 cc. and of the same bore and wall thick-
ness as the color standard tubes; and a 50 cc. bottle of the corre-
sponding indicator solution; a tube of distilled water; and a
pipette contained in a wooden case. The top of this case is so
designed that it may be removed and used as a comparator
block.
DETERMINATION OF HYDROGEN ION CONCENTRATION 299
back of the block between the three test tubes and the color
standards, and a piece of etched glass is placed on the outside
of the block directly over the three slots. This contrivance pro-
vides standard conditions of illumination at all times. Ampoules
of distilled water, bottles of indicator solution, graduated test
tubes, and pipettes are a part of the comparator equipment.
Any three sets of color standards such as chlorphenol red,
pH 5.2 to 6.8; bromthymol blue, pH 6.0 to 7.6; and phenol
red, pH 6.8 to 8.4 are placed in alternate holes in the revolving
drum in the order of their pH. Tubes of the same bore filled
with distilled water are then placed in the vacant holes. There
Exercise 91
Substance Concentration pH
Substance Concentration pH
they usually occur on the market, will falL Some deviations from
these values may, however, be expected, as the presence of even
a very slight excess of base or acid in these salts, or of carbon
dioxide in their solutions, exercises a pronounced influence upon
the hydrogen ion ·concentration.
304 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
References
1. BRITTON, "Hydrogen Ions," Chapman and Hall, Ltd., London, 1932.
2. CLARK, "The Determination of Hydrogen Ions," Williams & Wilkins
Press, Baltimore.
3. KOLTHOFF and FURMAN, "Potentiometric Titrations," John Wiley &
Sons, Inc., New York, 1931.
4. Leeds Northrup and Company Bulletins, Leeds Northrup and Company,
Philadelphia.
CHAPTER XIX
ELECTROLYTIC METHODS
Quantitative analysis by means of electrolysis, or electro-
analysis, as it is more generally called, is usually restricted to the
determination of metals. This method of analysis is based upon
the fact that an electrical current passed through a solution of
the salt of a metal causes the deposition of the metal, usually
in the elemental state, upon one of the electrodes. The electro-
lytic method may be applied to a number of official substances,
namely, mercury and its salts and the salts of silver, copper, and
zinc.
Electrical Units and Fundamental Laws.-The unit of current
is the ampere, that of resistance is the ohm, and that of difference
of potential or el~ctromotive force is the voU. The ampere is
the strength of current which when passed through a solution of
silver nitrate under certain standard conditions will deposit 0.001118
Gm. of silver per second. The ohm is defined as the resistance
offered to an unvarying electric current by a column of mercury
106.3 cm. long and 1 sq. mm. in cross-section at 0°0. The voU
is the electromotive force necessary to force a current of one ampere
through a resistance of one ohm. The relationship between the
ampere, volt, and ohm is expressed in Ohm's law, viz.: The
strength of an electric current flowing through a conductor is directly
proportional to the difference of potential between the ends of the
conductor and inversely proportional to its resistance. If C repre-
sents the strength of the current in amperes, E the difference of
potential in volts, and R the resistance in ohms, Ohm's law may
be formulated as follows:
E
C = Ii or, transposed, E = OR
Decomposition
Ion Metal
voltage
voltage below 2.12 and above 0.27. The greater the difference is
between the decomposition voltages of two metallic ions the easier
it is to separate them by electrolysis. In general, it may be said,
that the decomposition voltages of two substances must differ
by at least 0.2 to 0.3 volt in order to permit their separation by
electrolysis.
Electrolytic methods of assay are not so simple as is implied
in the foregoing examples, since numerous factors complicate
conditions, viz., resistance of the solution, polarization, over-
voltage, reactions at the electrodes, the nature of the solutions
used, the current density, the rate of stirring, the shape and size
Exercise 92
The copper ions migrate to the cathode where each copper ion
gains two electrons and is reduced to metallic copper. The
sulfate ions migrate to the anode where they react with hydroxyl
ions from the water, forming molecular oxygen and sulfuric
acid:
After stopping the current, detach the cathode cup and wash it
thoroughly with water, alcohol, and ether successively, dry it in
an electric oven or. air bath for 2 or 3 min. at 80 to 100°C., allow
the cathode to cool in a desiccator, and weigh it. The operations
of drying and weighing should be performed as quickly as possi-
ble, since the copper is subject to oxidation upon exposure to air.
After weighing the cathodc with the copper deposit, dissolve the
deposit completely by treating it with two successive portions
of about 10 cc. of concentrated nitric acid mixed with about
10 cc. of water using gentle heat to effect solution. Wash the
electrode successively with distilled water, alcohol, and ether
and dry again at 80 to 100°C., allow it to cool in a desiccatbr,
and weigh it again. The difference between the weight of the
cathode and the weight of the cathode with the copper deposit
is equal to the weight of copper deposited. The cathode may
be weighed before the electrolysis is started and again after the
deposition of the copper is complete, but this procedure leads to
a slight inaccuracy since the anode dissolves slightly during the
electrolysis and the dissolved platinum is plated out on the
cathode.
Calculate the percentage Cu, CUS04, and CuS04.5H 20 to
which the sample assayed corresponds.
Questions and Problems
1. Explain how oxidation and reduction are involved in the assay of copper
sulfate.
2. Why is the electrolyte acidulated with sulfuric acid?
3. Why is the solution of electrolyte stirred?
4. Why should the current not be stopped until the acid electrolyte has
been washed out of the cathode dish?
5. How many coulombs of electricity would be required to completely
deposit the copper from 0.6 Gm. of pure CuS04.5H 20?
Exercise 93
Object.-Assay of Mercuric Chloride.
Materials Required.-An electrolytic apparatus with a mercury cathode
cup.
316 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Grams
equivalent
Amount Amper-
Voltage to 1 Gm.
Substance used, age
used of
grams used
deposited
metal
U.S.P.
Copper sulfate ............ 0.75 to 1.0 2.5 5 to 7 3.9281
Copper sulfate, anhydrous 0.50toO.75 2.5 5 to 7 2.5112
Mercury ................. 0.2 to 0.3 1.5 to 2 7 to 10 1.0000
Mercury, ammoniated ..... 0.5 to 0.6 2 to 3 7 to 10 1.2566
Mercury bichloride ....... 0.3 to 0.4 1 to 3 8 to 12 1.3535
Mercuric iodide, yellow .... 1.0 to 1.2 2 to 3 7 to 10 2.2654
Mercuric oxide, yellow .... 0.2 to 0.3 1.5 to 2 7 to 10 1.0798
Mercuric salicylate ........ 0.7 to 0.8 2 to 3 7 to 10 1.1798
Mercurous chloride, mild .. 0.5 to 0.6 2 to 3 7 to 10 1.1768
Mercurous iodide, yellow .. 0.7 to 0.8 2 to 3 7 to 10 1.6327
Mercury with chalk ....... 0.6 to 0.8 1.5 to 2 7 to 10 1.0000
Silver nitrate ............. 0.3 to 0.5 2"5 5 to 7 1.5748
Silver nitrate, toughened... 0.3 to 0.5 2.5 5 to 7 1.5748
Zinc acetate .............. 0.5 4 to 5 5 to 6 3.3570
Zinc chloride ............. 0.3 4 to 5 5 to 6 2.0849
Zinc oxide .. ,.............. 0.2 4 to 5 5 to 6 1.2448
.zinc sulfate .............. 0.6 4 to 5 5 to 6 4.3988
Zinc sulfate, anhydrous .... 0.4 4 to 5 5 to 6 2.4695
N.F.
Mercuric iodide, red ....... 1.0 to 1.2 2 to 3 7 to 10 2.2654
Mercuric oxide, red ....... 0.2 to 0.3 1.5 to 2 7 to 10 1.0798
Zinc phenolsulfonate ...... 1.2 4 to 5 5 to 6 8.5011
'PART III
SPECIAL METHODS USED IN OFFICIAL
PHARMACEUTICAL ANALYSES
Quantitative analyses of crude drugs and of the products
derived from them are made to establish purity or to determine
the amount of therapeutically active constituents present for
the purpose of standardization. The special methods employed
in the analyses of this type may be classified as follows:
Chemical methods such as those employed in the determination
of ash, moisture, crude fiber, extractive obtained with different
solvents, the estimation of alkaloidal content, etc.
Physiological methods or those in which the effects upon
animals or animal tissues are measured and which are employed
in the absence of satisfactory chemical methods for standardiza-
tion. The official drugs assayed by physiological methods are:
U.S.P. aconite, tincture of aconite, cod liver oil, non-qestearinated
cod liv:er oil, digitalis, digitalis powder, tincture of digitalis,
solution of epinephrine, solution of irradiated ergosterol, ergot,
fluidextract of ergot, extract of liver, solution of liver, purified
solution of liver, solution of parathyroid, solution of posterior
pituitary, stomach, and strophanthin and tests for the toxicity
and purity of arsphenamine, neoarsphenamine, and tryparsamide;
N.F. fluidextract of aconite, convallaria root, fluidextract of
convallaria root, ampuls of epinephrine hydrochloride, extract of
ergot, ampuls of posterior pituitary, fluidextract of squill, stro-
phanthus, tincture of strophanthus, and suprarenal. Physio-
logical methods require special apparatus for their performance
and a technique which is not chemical in nature; hence, a dis-
cussion of them does not fall within the scope of this text.
CHAPTER XX
ASH AND MOISTURE DETERMINATIONS
Ash Content.-Th~ ash content of a crude drug is generally
taken to be the residue remaining after incineration. It usually
represents the inorganic salts naturally occurring in the drug and
adhering to it, but it may also include inorganic matter added
for the purposes of adulteration. There is a considerable differ-
ence in the ash content of different drugs, but the difference varies
within narrow limits in the case of the same individual, hence an
ash determination furnishes a basis of judging the identity and
cleanliness of a drug and gives information relative to its adultera-
tion with inorganic matter. Ash standards have been established
for a number of the official drugs; usually these standards set a
maximum limit on the total ash or on the acid-insoluble ash
permitted. The total ash is the residue remaining after incinera-
tion, while the acid-insoluble ash is that part of the total ash
which is insoluble in diluted hydrochloric acid. The Pharma-
copoeia specifies that all vegetable drugs shall be separated by
mechanical means in so far as possible from lumps of dirt or other
foreign inorganic matter before they are ground or powdered.
When no ash standard is fixed for a given drug by the Pharma-
copoeia or National Formulary, the amount of foreign inorganic
matter estimated as acid-insoluble ash must not exceed 2 per
cent of the weight of the drug.
Tpe ash or residue yielded by an organic chemical compound
is as a rule a measure of the amount of inorganic matter present as
impurity. In most cases, the inorganic matter is present in
small amounts which are difficult to remove in the purification
process and which are not objectiohable if only traces are present.
The careful control of temperature is the most important
analytical factor to regulate in making ash determinations. All
determinations should be made in such a manner as to duplicate
in so far as possible the conditions under which standards are
established. When an electric furnace is used for ignitions, the
323
324 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
3. Why should the incineration residue not be heated above a dull redness?
4. Name the important inorganic plant constituents which will not be
found in the ash.
6. What does the quantity of acid-insoluble ash in a drug indicate?
>Acid- Acid-
Total insolu- Total insolu·
ash. ble ash, ble
Substance Substance
per ash, per ash.
cent per cent per
cent cent
U.S.P. U.S.P.
Acacia ................ . 4.0 0.5 Digitalis ............. " 5.0
Acetanilid .......... . 0.05 Elaterin ............... . 0.1
Acetophenetidin. . . .. . .. 0.05 Ephedrine ............. . 0.1
Acid. acetylsalicyhc.. .. 0.05 Ephedrine hydrochloride. 0.1
Acid. acetyltannic.. .. 0.3 Ephedrine sulfate ...... . 0.1
Acid. benzoic .. . 0.05 Ethyl aminobenzoate .. . o1
Acid, citric .. .......... . 0.05 Glucose .............. " 0.5
Acid lactic.. . . . ..... . 0.12 Glycerin .............. . 0.007
Acid. oleic... ... . . . .. .. 0.10 Glycyrrhiza ............ . 2.5
Acid. salicylic .......... . 0.05 Glycyrrhiza. extract of .. . 8.0
Acid. tannic ........... . 0.5 Guaiacol. ............ . 0.1
Acid. tartaric .......... . 0.05 Hyoscyamus . .......... . 12.0
Acid. trichloroacetic ... . 0.05 Iodoform .............. . 0.2
Agar ................. . 1.0 Iodine .............. . 0.05
Albumin tannate. 0.3 Lactose ...... ....... . 0.1
Aloe .................. . 4.0 Menthol. ........... . 0.05
Aloin .............. . 0.5 Mercuric chloride 300°C. 0.1
Aminopyrine . .......... . 0.1 Mercuric oxide, yellow .. . 0.2
Ammonium benzoate .. . . 0.05 Mercuric salicylate . .... . 0.2
Ammonium bromide . ... . 0.05 Mercurous chloride . .... . 0.1
Ammonium carbonate. 0.05 Mercurous iodide, yellow 0.2
Ammonium chloride ... . 0.1 Mercury .............. . 0.02
Ammonium salicylate ... , 0.05 Mercury, ammoniated. 0.2
Antipyrine ............ . 0.1 Mercury succinimide . .. . 0.1
Asafoetida .......... '" 15.0 Methenamine .......... . 0.05
Aspidium ............. . 3.0 Methylthionine chloride. 1.0
Belladonna leaf. ...... . 3.0 Myristica ............. . 0.5
Belladonna root ... . 4.0 Myrrh ................ . 4.0
Benzoin, Sumatra .. 1.0 Paraffin, chlorinated .... . 0.1
Benzoin, Siam .... . 0.5 Petrolatum ............ . 0.05
Betanaphthol. ... . o 05 Petrolatum. white ...... . 0.05
Caffeine ........... . 0.05 Phenacaine hydrochloride 0.1
Caffeine, citrated . .. . 0.1 Phenol. ............... . 0.05
Camphor ......... . 0.05 Phenol. liquefied. . . .. .. 0.05
Cannabis ....... . . 5.0 Phenolphthalein ....... . 0.05
Capsicum ......... . 1.25 Phenolsulfonphthalein .. . 0.2
Cardamom seed. 5.0 Phenyl salicylate ....... . 0.05
Caraway ..... . 1.5 Pi~ tar ............... . 0.25
Charcoal. activated ... . 4.0 Prepared chalk ........ . 2.0
Chloral hydrate ........ . 0.05 Pyrogallol. ............ . 0.1
Chlorobutanol. " ... . 0.1 Quinidine sulfate ....... . 0.1
Chrysarobin ........... . 0.25 Qninine ............... . 0.1
Clove ............... . 0.75 Quinine ethyl carbonate. 0.2
Cotton. purified ........ . 0.2 Quinine and urea hydro-
Creosote carbonate ..... . 0.1 chloride ............. . 0.05
Dextrose ... . 0.1 Quinine bisulfate .. 0.05
328 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Acid- Acid-
Total insolu- Total insolu-
ash, ble ash, bIe
Substance Substance
per ash, per ash,
cent per cent per
cent cent
U.S.P. N.F.
Quinine dihydrochloride. 0.05 Colocynth ............. . 6.0
Quinine suliate ......... . 0.05 Convallaria root ....... . 6.0
Resin of podophyllum .. . 1.5 Coriander ............. . 1.5
Resorcinol. ............ . 0.05 Corpus luteum...... .... 6.0
Resin ................. . 0.05 Crocus................. 7.5 1.0
Saccharin, soluble ...... . 0.5 Cudbear. . . . . . . . .. .... 12.0
Santonin .............. . 0.1 Damiana .............. . 4.0
Sarsaparilla, Mexican ... . 4.0 Euonymus ............ . 4.0
Senna ................. . 3.0 Euphorbia ............. . 3.0
Serpentaria ............ . 10.0 Fennel. ............... . 1.5
Starch ................ . 0.5 Gambir ............... . 0.5
Stramoni UIn .. . . . . . . . . . . 4.0 Gamboge .............. . 1.0
Strychnine sulfate ...... . 0.1 Guaiacol carbonate...... 0.1
Sucrose ............... . 0.05 Guarana .............. . 0.5
Sulfonethylmethane .... . 0.05 Humulus .............. . 5.0
Sulfur, precipitated ..... . 0.3 Hydrastis ............. . 3.0
Sulfur, sublimed ........ . 0.5 IchthammoI........ .... 0.5
Sulfur, wl..shed ......... . 0.3 Ipomoea .............. . 3.0
Terpin hydrate ......... . 0.05 Iris .......... ......... . 1.0
Theophylline with eth- Jalap ............ -..... . 0.5
ylene diamine . ....... . 0.1 Kamala .............. . 6.0
Thymol. .............. . 0.05 Kola .................. . 0.5
Thymol iodide ......... . 1.5
Valerian ....•.......... 10.0
Leptandra .......... , .. .
Lobelia ............... .
1::::: 6.0
5.0
Vanillin ............... . 0.05 Lupulin ............... . 10.0
Veratrum viride .•....... 4.0 Mastic ................ . ,..... 0.25
Wool fat .....•......... 0.1 Matricaria . ........... . 4.0
l"I.1". Mullein leaves ......... . 4.0
Acid, gallic ...•......... 0.1 Ovary and ovarian resi-
Aletris ................ . 10.0 due ................. . 7.0
Animal charcoal, purified 4.0 Pimenta .............. . 0.4
Anise ................. . 1.5 Pituitary, R"lterior ... , ..
7.0
Areca ................. . 2.5 Pituitary, whole ....... . 7.0
Brucine sulfate ......... . 0.1 Plantago seed .......... . 4.0 1.0
Buchu ................ . 1.0 Poplar bud ............ . 1.0
Calamus .............. . 6.0. 0.5 Quassia ............... . 0.5
Calumba .............. . 2.5 Resin. ipomoea . ..... , .. 0.5
Camphor ,monobromated 0.05 Rose ................. . 1.0
Caramel. .............. . 8.0 Salvia ................ . 10.0 1.0
Carmine .............. . 12.0 Sassafras .............. . 5.0
CauolphYIlum ......... . 4.0 Sassafras pith .......... . 0.5
Celery fruit ............ . 3.0 Strychnine ............ . 0.1
Chlorthymol. .......... . 0.05 Suifonemethane ........ . 0.05
Cimicifuga ............ . 4.0 Suprarenal. ........... . 7.0
Cinchouine sulfate ..... . 0.1 Taraxacum ............ . 4.0
Cinchonidine sulfate .... . 0.1 Thyme ..... " ......... . 4.0
Cinchophen ........... . 0.25 Triticum ....... ' ...... . 3.0
Coal tar .............. . 2.0 Ulmus ................ . 1.0
Colchicum corm .•...... 0.5 Viburnum prunifolium .. . 3.0
ASH AND MOISTURE DETERMINATIONS 329
TABLE XLVI.-SOME OFFICIAL SUBSTANCES WITH RESIDUE REQUIREMENTS
U.S.P.
Acetone ...... " ................ " 50 100 0.002
Acid, acetic ....................... 20 100 0.002
Acid, diluted hydriodic ............. 5 Ignite 0.100
Acid, hydrochloric ................. 10 Ignite 0.002
Acid, nitric ....................... 30 Ignite 0.002
Acid, sulfuric ..................... 2 Ignite 0.001
Alcohol. .................... '" '" 40 100 0.001
Benzin, petroleum ................. 50 40 0.001
Ether ............................ 50 100 0.001
Ethyl oxide ....................... 50 100 0.001
Water,
ammonia ....................... 10 100 0.002
distilled ........................ 100 100 0.001
distilled, sterilized ............... 100 100 0.001
orange flower ................... 100 100 0.001
rose, stronger ................... 100 100 0.001
N.F.
Antiseptic solution ................. 10 100 0.184
Water ............................ 100 100 0.030
Water, hamamelis ................. 100 100 0.025
Water, redistilled ... , .............. 100 100 0.0005
Exercise 95
Exercis~ 96
Object.-Determination of the Moisture Content of Digitalis
by the Toluene Distillation Method.
Materials Required.-50 Gm. of digitalis leaf.
Toluene Moisture Apparatus.-Use a 500 cc. flask preferably of Pyrex
glass, a straight tube Liebig condenser of about 500 mm. length, and a
332 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
moisture-tube receiver calibrated to 0.1 cc. of the type illustrated (Fig. 59).
Clean the condenser and moisture tube with cleaning mixture (see page 5),
rinse with distilled water and then with alcohol, and dry them in an oven at
100°C.
Procedure.-l. "Place in the flask an accurately weighed amount of the
drug to be tested, which it is estimated will yield from 2 to 4 cc. of water.
If the drug is likely to cause bumping, add enough dry sand to cover the
bottom of the flask. Add sufficient toluene to cover the drug
completely, usually about 75 cc., and connect the apparatus
as illustrated. Fill the receiving tube with toluene by pquring
it through the top of the condenser. Heat the toluene in the
flask until it boils, and distil slowly, about 2 drops per second,
until most of the water has passed over; then increase the
rate of distillation to about 4 drops per second."
Sufficient drug must be taken to yield from 2 to 4
cc. of water because smaller amounts would be
difficult to determine without a relatively large per
cent error. Thus an error of 0.05 cc. in the cali-
bration or reading of the moisture tube would cause
an error of 5 per cent if only 1 cc. of water is
obtained and of 1.25 per cent if 4 cc. of water is
obtained. At the boiling point of t'oluene, 110 to
FIG. 59.- 111 ce., the moisture in the drug is volatilized.
Assembled The moisture distils with the toluene, ana as the
apparatus for
moisture de- vapors condense and drop into the moisture tube,
termination the water which is immiscible with and heavier than
by toluene
distillation. toluene separates and collects at the bottom of the
moisture tube.
2. "When the water is apparently all over, wash down the condenser
by pouring toluene in at the top, continuing the distillation a short time to
ascertain whether any more water will distil, and if it does, repeat the wash-
ing of the condenser with toluene. If any water remains in the condenser,
remove it by brushing it down into the tube receiver with a tube brush
attached to a copper wire and saturated with toluene, at the same time
washing the condenser with toluene. Allow the receiving tube to stand
until cooled to room temperature and if any' drops of water still adhere to
the sides of the tube they can be forced down by a rubber band wrapped
around a copper wire. Finally read the volume of water and calculate to
determine the percentage which was present in the drug."
Tem- Tern ..
Moisture Moisture
per- per-
Substance limit, Substance limit,
ature, ature,
per cent per cent
°C. °C.
U.S.P. U.S.P.
Acacia .............. . 15 Phenolsulfonphthalein. 110 1
Acid acetyltannic. . . . . 100 3 Potassium carbonate . . 180 15
Acid. tannic.. . . . . . . . . 100 12 Potassium citrate . ... . 150 3 to 6
Acriflavine. . . . . . . . . . . 100 7 Potassium iodide. " .. . 100 1.5
Acr i II a vi ne, hydro- Potassium and sodium
chloride ............ H2S0, 7 tartrate .... ....... . 150 21 to 26
Agar ............... . 16 Quinidine sulfate. '" .. 120 5
Albumin tannate...... 100 6 Quinine ....... , ..... . 100 15
Aloe ................ . 10 Quinine bisulfate ..... . 100 24
Alum. exsiccated. . . . . . 200 10 Quinine dihydrochlo-
Barbital. soluble. . . . . . 100 1 ride .............. . 100 3
C~ffeine. .. . .. . . . . . . . . 80 9 Quinine ethyl carbon-
Caffeine. citrated. . . . . . 80 5 ate ............... . H2S0, 2
Caffeine with sodium Quinine sulfate ....... . 100 16.2
benzoate. . . . . . . . . . . 80 5 Scopolamine hydrobro-
Calcium iodobehenate. 100 2 mide .............. . 100 13
Calcium lactate... . . . . 120 25 to 30 SoaP ............... . llO 36
Cantharides. . . . . . . . . . 100 10 Soap. powdered ...... . llO 10
C ....ein. R...... . . . . . . 100 10 Soap, 8oft ........... . llO 52
Codeine.............. 80 6 Sodium acetate ...... . 120 36 to 41
Codeine sulfate. . . . . . . 100 12 Sodium biphosphate .. . 100 10 to 15
Dextrose. . . . . . . . . . . . . 105 10 Sodium carbonate. ..
Digitalis ............ . 8 monohydra ted ..... . 110 10 to 15
Digitali•• powdered ... . 5 Sodium citrate ... " .. . 150 10 to 13
Emetine hydrochloride 100 8 t<i 16 Sodium iodide ....... . 120 7
Ephedrine hydrochlo- Sodium phosphate ... . 110 43 to 50
ride ................ H2S0. 2 Sodium phosphate, ex-
Ephedrine sulfate. . . .. H2S0, 2 siccated ........... . 110 5
Ergot ............... . 8 Sodium stearate .... .. . 110 5
Ethylhydrocupreine Sodium sulfate ....... . 120 51 to 57
hydrochloride ...... H2S0, Sodium thiosulfate ... . 100 32 to 37
Ethylmorphine hydro- Starch .............. . 14
chloride.. .. . . . . . . . . 100 10 Strychnine sulfate .... . 100 11.5
Fluorescin. soluble. . . . 105 5 Theobromine with so-
Gentian ............. . 10 dium salicylate .. .. . 110 10
Glucose ............. . 90 21 Theophylline ........ . 100 9.5
Histamine phosphate .. 100 1 Theophylline with
Iodoform ............ . H2S0. 1 ethylene diamine ... . H,SO, 4.5
Magnesium oxide .... . Ignite 10 Thyroid ............. . 100 6
Magnesium sulfate .•.. Ignite 45 to 52 Tryparsamide ....... . 110 2.5 to 3.5
Merbaphen .......... . 100 2 " Wool fat ............ . 100 0.5
Methylthionine chlo- Wool fat. hydrous .... . 100 25 to 30
ride .............•. 110 16 N.F.
Morphine sulfate ..... . 130 12 Acid. gallic .......... . 100 12
Phenacaine hydrochlo- Aluminum sulfate .... . 200 45 to 49
ride .............. . 105 7 Ammonium hypophos-
Phenobarbital. ...... . 140 7 phite .............. H 2SO, 3
334 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Tem- Tem-
Moisture Moisture
per- per-
Substance limit, Substance limit.
ature, ature,
per cent per Qent
DC. DC.
- - - - - - - - -------11---------
N.F. N.F.
Ammonium iodide .. .. 110 6 Mercuric o)(ide. red. .. H2S0, 2
Ammonium valerate, Methyl-rosaniline. . . 110 7.5
acid ............ . H2S0. 2 Morphine hydrochlo-
Arecoline hydrobro- ride. . . . . . . . . . . . . . . 100 15
mide ............ . H2S0. Ovarian residue . ..... . 6
Brucine sulfate ...... . 100 13 Ovary .............. . 6
Calcium glycerophos- Papaverine hydrochlo-
phate ............. . 130 10 ride ............... H2S0.
Calcium hypophos- Pilocarpine hydrochlo-
phite ............. . H,SO. 3 ride ............... H,SO. a
Calcium phosphate ... . 200 4 Pituitary. anterior ... . 6
Carmine ............ . 100 25 Pituitary, whole .. . 6
Charcoal. purified ani- Potassium chloride. 100 1
mal. .............. . 100 12 Potassium guaiacolsul-
Cholesterol. R ....... . 100 2 fonate... .... H,SO. 2
Cinchonidine sulfate .. . 100 12 Potas::dum hypophos-
Cinchonine sulfate ... . 100 5 phite... . ...... . H,S04 Ii
Cinchophen ......... . 100 2 Potassium thiocyanate llO Ii
Corpus luteum ....... . 6 Quinine hYdrobromide. 100 5
Cotarnine chloride, .. . H,SO. 1 Quinine hYdrochloride. llO 10
Ethyl carhamate ... H,SO. 3 Quinine salicylate . ... . 100 5
Ferric glycerophos- Resin of ipomoea . ..... . 1100 i
phate ......... . 110 5 Resin of jalap .....•.. 100 4
Ferric hypo phosphite .. H,SO. 3 Sabal. .............. . 10 to 16
Hydrastine hydrochlo- Salicin.. .. . . . .... . H2S04 2
ride .............. . H,SO. 2 Sodium ",senate ..... . "150 3
Lithium benzoate .... . 100 3 Sodium hYllOphosphite. H,SO. 3
Lithium c,,,bonate ... . 100 2 Sodium sulfate ....... . 100 3
Li thi um citrate .... .. . 150 26 Sodium thiocyanate . . . llO .;
Lithium slllicyiate .... . 100 5 Sparteine sulfate ..... . 100 22
Manganese glycero- Strontium bromide ... . 200 32
phosphate......... . 110 10 Strontium salicylate .. . 3
Manganese hypophos- Sulfonmethane ....... .
phite ............. . H2S0. 2 Suprarenal . ......... . 6
Mercuric iodide, red .. . 120 1 Zinc iodide ........ . 5
Exercise 97
U.S.P.
Capsicum ............ . 12
Cinnamon .............. . 2
Clove ............... , .. . 15
Ginger ................. . 4.5
Ginger, fluidextract of ... . 20 4.5W/V
Linseed .............. , .. . 30
Myristica ......... , ..... . 25
N.F.
Cacao, prepared ......... . 22
Coriander ........ , ..... . 0.5
Cubebs ................. . 10
Kamala ............... . 70
LupuIin .. " .......... '" 60
Mastic ................. . 97
Salvia ............ , ..... . 1.0
Sandalwood, white ....... . 3.5
EXTRACTIVE AND CRUDE FIBER CONTENT 339
hours and weigh the total ether extract. Now heat the extract gradually
up to 110°C. until the weight becomes constant; the loss in weight during
the heating represents the,volatile portion of the extract."
method, page 331, calculate the weight of moisture in the Benzoin and sub-
tract this weight of moisture from the original weight of the Benzoin taken
for the assay. The difference between this result and the weight of the
residue determined above represents the alcohol-soluble extractive."
U.S.P. I
Asafoetida .............. 94 50
Benzoin, Sumatra ........ 94 75
Benzoin, Siam ........... 94 90,
Bismuth and potassium
tartrate ............... 94 (n.m.t.) 0.5
Bismuth subgallate .... '" 94 (n.m.t.) 0.5
Kino ................... 94 60
Myrrh .................. 94 30
Rhubarb ................ 49 30
N.F.
Chionanthus .. ' .......... 73 25
Gamboge ............... 94 65
Gambir ................. 94 60
Guaiac ................. 94 85
Manna ................. 94 75
Mastic ............... '" 95 80
Poplar bud .............. 95 40
Vanilla ................. 49 12
benzoic acid in the free state, an acid value of less than 112 would
indicate that the acid content of the balsam was low and thll.t it
was of inferior quality or adulterated. On the other hand, an
acid value greater than 168 would indicate adulteration with
some substance having high acid value, such as certain resins.
Exercise 101
Object.-To Determine the Acid Value of Rosin.
Materials Required.-About 1 Gm. of rosin.
0.5 N potassium hydroxide.
About 50 cc. of alcohol.
Procedure.-l. Pulverize the rosin in a mortar and dissolve about 1 Gm.
of the powder, accurately weighed in from 40 to 50 cc. of neutral alcohol.
Substance
Amount
used,
Alkali
- Official
rtquircment,
used
Gm. cid value
U.S.P.
Acid, oleic ................ 10 0.1 N NaOH 188 to 200
Copaiba .................. 2 0.5NKOH 28 to 95
Peruvian balsam .......... 1 0.5 N NaOH 56 to 84
Rosin ................... 10 0.1 N NaOH Not less than 150
Soap, hard (acids) ......... 10 0.1 N NaOH 185 to 205
Soap, soft (acids) .......... 10 0.1 N NaOH 190 to 205
Storax, American .......... 1 0.5 N NaOH 38 to 85
Storax, Levant ............ 1 0.5 N NaOH 56 to 85
Tolu balsam ........ I • • . • • 1 0.5NKOH 112 to 168
(alcoholic)
White wax ................ 3 .0.5 NKOH 17 to 23
(alcoholic)
Yellow wax ............... 3 0.5NKOH 18 to 24
(alcoholic)
N.F.
Mastic ................... 10 0.1 N NaOH Not less than 50
Resin of ipomoea .......... 2 0.5 NKOH 8.5 to 18
CONSTANTS OF FATS, FATTY OILS, WAXES, ETC. 349
o. If a 2 Gm. sample of cod liver oil required 4.5 cc. of 0.02 N NaOH in
the titration of the free fatty acids, would the oil conform to the official
purity requirement? What would be the acid number of the oil?
6. Calculate the minimum and maximum acid values permitted under
the tests for purity of chaulmoogra oil.
In addition to the listed substances for which definite acid
value limits are given in the official standards, there are a number
of substances for which the maximum content of free fatty acids
is fixed by the volume of the standard alkali solution required
in their titration; e.g., 2 Gm. of cod liver oil must require not
more than 1 ee. of 0.1 N NaOH, and 1 Gm. of prepared suet
should not require more than 0.6 cc. of 0.1 N NaOH to neutralize
the free fatty acids.
Saponification Value.-The saponification value, saponification
number, or Koettsdorfer number, as it is sometimes called from
the originator of the process, is defined as the number of mt'lligrams
of potassium hydroxide required to neutralize the free acids and
saponify the esters contained in 1 Gm. of oil, fat, wax, or other
substance of similar composition. This value represents the
amount of potassium hydroxide, expressed in tenths of 1 per cent,
required to neutralize the total free and combined acids in 1 Gm.
of the substance, or, in other words, it is ten times the percentage
of potassium hydroxide required to neutralize all of the acids
contained in the sample afte.r saponification. Since the natural
fats and oils consist of mixtures of glyceryl esters of the higher
acids, their saponification values do not differ greatly. The
determination of the saponification value, however, serves to aid
in the detection or" the presence of the glycerides of acids con-
taining less than 16 or more than 18 carbon atoms, since the value
of this constant is inversely proportional to the mean molecular
weights of the acids present. In some. cases, it may a,_lso indicate
adulteration of the sample with ul,lsaponifiable matter, such as
mineral oil.
Exercise 102
Object.-To Determine the S'aponification Value of Cottonseed
Oil.
Materials Required.-2 Gm. of cottonseed oil.
50 cc. of 0.5 N alcoholic potassium hydroxide (see page 365).
About 50 cc. 0.5 N hydrochloric acid.
350 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
"If the oil has been saturated with carbon dioxide for the purpose of pres-
ervation, it should be exposed in a shallow dish in a vacuum desiccator for
twenty-four hours before the portions are weighed for this determination."
Procedure.-l. Place from 1.5 to 2 Gm. of the sample, accurately weighed,
in a flask of from 200 to 250 cc. capacity, and add to it exactly 25 cc. of
alcoholic 0.5 N potassium hydroxide. rnsert into the neck of the flask, by
means of a perforated stopper, a glass tube from 70 to 80 cm. in length and
from 5 to 8 mm. in diameter, and heat the flask on a water bath for 72' hr.,
frequently rotating the contents.
3. Make a blank test at the same time, using exactly the same amount
of alcoholic 0.5 N potassium hydroxide. The difference in the number o~
cubic centimeters of 0.5 N hydrochloric acid consumed in the actual test
and the blank, multiplied by 28.06 and divided by the weight of the sample
taken, gives the saponification value.
Amount Saponifi-
Substance us~sl, cation
Gm. value
o \
U.S.P.
Balsam of Peru ................ 3 235 to 238
Castor oiL .................... 1.5 to 2 179 to 185
Chaulmoogra oil. .......... ... 1.5 to 2 196 to 213
Cod liver oil. .................. 1.5 to 2 180 to 192
Corn oil. ..................... 1.5to2 188 to 193
Cottonseed oil. ................ 1.5to2 190 to 198
Ethyl chaulmoograte ........... 1.5to2 190 to 196
Expressed oil of almond ......... 1.5 to 2 191 to 200
Lard ......................... 1.5to2 195 to 203
Linseed oil. ......... , ........ 1.5to2 187 to 195
Oil of thedbroma ............... 1.5to2 188 to 195
Olive oil. ............ o •••••••• 1.5to2 190 to 195
Prepared suet ................. 1.5to2 193 to 200
Storax ........................ 1.5 to 2 160 to 200
Tolu balsam ................... 1 154 to 220
N.F.
Croton oil ................... ~ . 1.5 to 2 200 to 215
Resin of ipomoea .............. 1.5to2 170 to 190
Sesame oil. ................... 1 188 to 193
CONSTANTS OF FATS, FATTY OILS, WAXES, ETC. 353
the ether just to dryness on a water bath, and dry the residue for
30 min. at 100°C. Cool the beaker in a desiccator for 30 min.,
and weigh the residue of unsaponifiable matter.
The Pharmacopoeia requires that both cod liver oil and linseed
oil should not contain more than 1.5 per cent and that corn oil
should contain not more than 2 per cent of unsaponifiable matter.
Iodine Value.-The iodine value, or number, is the number of
grams of iodine absorbed by 100 Gm. of oil, jat, wax, or other sub-
stance under specified conditions. This value is a quantitative
measure of the proportion of unsaturated fatty acids present,
both free and combined as esters, which have the property of
absorbing iodine.
The determination of the iodine number of fats and oils is
important, since it serves to characterize them and to indicate
whether they are pure or admixtures. The so-called drying oils,
such as linseed oil, and the fish oils, such as cod liver oil, have
very high iodine numbers, usually above 120, since they contain
a large proportion of unsaturated fatty acids; the non-drying oils,
such as olive oil and almond oil, have relatively low iodine
numbers, below 100; and the semidrying oils, such as cottonseed
oil and sesame oil, have intermediate iodine values, that is,
between 100 and 120. In the case of the animal fats, the iodine
number is not very high, usually being less than 90. The deter-
mination of the iodine number, therefore, not only serves as an
aid to the identification of known oils, but it also serves to indi-
cate in a definite manner the class to which an unknown fat or
oil belongs. Furthermore, when the iodine number is considered
in conjunction with the saponification value of a fat or oil, it
serves as a means of detecting adulteration, and frequently it
indicates the nature of the adulterant; e.g., olive oil might be
adulterated with cottonseed oil without changing -the saponifica-
tion value appreciably, but the iodine number of the olive oil
would be increased. Again, castor oil might be adulterated
with olive oil without changing the iodine number greatly, but
the saponification value of the castor oil would be increased.
Several methods have been developed for the determination
of the iodine number of fats and oils. These methods are
generally designated by the name of their originators, as, for
example, the Hubl, Hanus, and Wijs methods. The method
356 QUANTITATIVE PHARMACEUTICAL CHEMIS7'RY
Exercise 103
Object.-To Determine the Iodine Value of Olive Oil.
Materials Required.-About 1 Gm. of olive oil.
20 cc. of chloroform.
50 cc. of iodobromide test solution.
60 cc. of potassium iodide test solution.
About 100 cc. of 0.1 N sodium thiosulfate solution.
Starch test solution.
Procedure.-1. "Introduce about 0.8 Gm. of a solid fat or about 0.3 Gm. ~
of an oil, accurately weighed, into a glass-stoppered flask or bottle of 250-cc.
capacity, dissolve it in 10 cc. of chloroform, add 25 cc. of iodobromide T.S.,
accurately measured from a burette or pipette, stopper the vessel securely,
and allow it to stand for thirty minutes t in a cool place protected from light."
The blank test, when carried out under the same conditions
as the actual test, corrects for the presence of impurities in the
reagents, changes in volume at different temperatures, etc.,
and makes it unnecessary to know the exact normality Of the
iodobromide test solution. The blank test should be carried out
CONSTANTS OF FATS, FATTY OILS, WAXES, ETC. 359
the qualitative tests for the various substances which are com-
monly employed as adulterants. Only the official quantitative
procedures will be discussed here.
Methods of General Application.-The purity and quality of
volatile oils may be judged to some extent by their appearance,
odor, color, etc.; but the information gained from the determina-
tion of the specific gravity, rotatory power, refractive index,
solidifying point, solubility, and behavior on distillation is of
much greater importance.
Specific Gravity.-The specific gravity of a volatile oil may be
determined with the Westphal balance or pycnometer, the
latter being the more accurate method of the two, and expressed
as the ratio of the weight of the volume of oil to that of an equal
volume of pure water when both are determined at 25°C. (see
page 217).
The specific gravities of the official volatile oils vary approxi-
mately between 0.84 and 1.2. Those oils which are lighter
than water are usually rich in hydrocarbons, alcohols, esters,
aldehydes, and ketones, such as oil of orange, caraway, coriander,
lemon, turpentine, and rosemary. Oils the spt;;_cific gravities of
which approach or exceed 1.0 usually contain chiefly phenols,
phenolic derivatives, or certain esters, e.g., oil of anise'lcinnamon,
clove, sassafras, and mustard.
The specific gravity of any volatile oil is not absolutely con-
stant, since it is influenced by such factors as the matl,J.rity of the
plant from w!ich the oil is obtained, as well as the method of
preparation, purification, and age of the oil.
Rotatory Power.-The rotatory power of a volatile oil is
generally measured with a Laurent half-shadow polarimeter,
according to the procedure described on page 247, using sodium
light and a tube 10 cJ?1. long, but for highly colored oils, tubes 5
or even 2.5 cm. long may be used. The observation of the
optical activities of the official essential oils should be made at
25°C. Slight deviations from this temperature do not greatly
affect the rotatory power of a volatile oil, except in the case of oil
of lemon and oil of orange.
The rotatory power of some of the volatile oils varies within
relatively wide limits. This determination should never be
omitted in their examination, however, since it frequently serves
ASSAY OF VOLATILE OILS 363
as a valuable means of detecting adulteration with inactive sub-
stances, such as alcohol t or with substances of different rotatory
power from that of the oil being examined, e.g., oil of lemon
(+57 to +64°) adulterated with oil of turpentine (about +25 to
-40°).
Refractive Index.-The refractive index of a volatile oil is
most commonly determined by means of an Abbe refractometer,
as described on page 240. The measurement of the refractive
indices of all of the official volatile oils should be performed at
20°C. The index of refraction does not vary greatly with
different official volatile oils, the values being between about
1.46 and 1.61 at 20°C. In some cases, this determination may,
however, serve for the detection of extraneous matter.
Congealing Point.-The congealing point of a volatile oil is
determined by the method described on page 231. Most essen-
tial oils solidify only at low temperatures, consequently in
practice, this determination is carried out with only a few oils,
such as oil of anise and oil of fennel, which contain large amounts
of the readily crystallizable constituent anethol. The higher
the congealing point of these oils the more they are valued.
An abnormally low congealing point of an essential oil indicates
the partial removal of the characteristic constituent for which
the oil is valued or the addition of extraneous matter, such as
alcohol.
Distilling Point.-The distilling point of a volatile oil is
determined by the general method described on page 234.
Volatile oils which are composed of mixtures of hydrocarbons,
alcohols, esters, etc., do not have a fixed boiling point but boil
between certain limits of temperature, frequently separated
widely. Consequently, the official standards usually designate
the temperature or range of temperature at which a definite
percentage of the oil distils; e.g., 90 per cent of oil of turpentine
should distil between 154 and 170°C., and less than 10 per cent of
oil of dwarf pine needles should aistil below 165°0.
Fractional Distillation.-Fractional distillation is resorted to
occasionally in the official tests for purity of volatile oils. It
serves either to' separate the various components of volatile oils
or to detect adulteration. Thus, alcohol and petroleum ether,
both of which boil below 100°0., may be separated and identified
364 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
6
A -(}--G--CH, + KOH____'~H + CH,COOK
o
'\- '
2. "Allow the mixture to cool, disconnect the flask from the condenser,
and titrate the excess of alkali with half-normal sulfuric acid, using 10
ASSAY OF VOLATILE OILS 367
3. What factor would be necessary for the ester in order to obtain the
per cent of total esters directly as described above if the chief ester present
in an oil was bornyl acetate; linalyl acetate? Show how these factors are
derived. .
4. Note the equivalents given in the following table for linalyl acetate in
oil of lavender, U.S.P., and in oil of bergamot, N.F. Which is correct?
368 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
6 .
water liberated in the side reaction:
-OH
0
~
+ H0-C--CHs-
o
'\,
O-G-CHs + HOH
A
2. "When the liquids have completely separated, reject the aqueous layer,
and wash the remaining oil with successive portions of sodium carbonate
T.S., diluted with an equal volume of distilled water, until the washing is
alkaline to 2 drops of phenolphthalein T.S. Dry the resulting Oil with
anhydrous sodium sulfate (prepared by drying sodium sulfate to constant
weight at 110°C. and powdering), and filter it."
370 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
The oil is washed with sodium carbonate test solution (12.5 Gm.
of Na2,C0 3 .H2,O ,in sufficient distilled water to make 100 ce.) to
neutralize the excess acetic acid. The washed oil is then dried
over anhydrous sodium sulfate to remove the small amounts of
alkaline sodium carbonate solution which it contains.
3. "Transfer 5 cc. of the dry acetylilled oil to a tared, 100-cc. Erlenmeyer
flask, note its exact weight, add 50 ce. of half-normal alcoholic potassium
hydroxide, connect the flask with a reflux condenser, and boil the mixture
on a water bath for one hour."
1. Having determined the ester value and 'the percentage of total borneol
present in oil of rosemary, how could the percentage of free borneol be
found? Give an example.
;372 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
2. Write the reactions which take place in the assay of oil of rosemary for
total borneol.
3. If oil of peppermint containing 7.2 per cent of total esters is found to
contain 51.5 per cent of total menthol (uncorrected), what change in the
result would the correction 1 - (E X 0.0021) cause? Is this correction
important?
TABLE LVI.-OFFICIAL VOLATILE OILS ASSAYED FOR THEIR ALCOHOL
CONTENT
Amount of Equivalent
acetylized of 1 cc. of Official require-
Oil Correction factor
oil used, 0.5 N KOH, ment, per cent
Gm. Gm,
U.S.P.
Oil of peppermint ... 5 0.07808 1 - (E X 0.0021) Menthol
ClOH"OH =50
Oil of rosemary ..... 5 0.0771 1 - (E X 0.0021) Borneol
ClOH170H = 10
Oil of Ban tal. ....... 5 0.1101 None Santalol
C"H"OH = 90
O '"
H
+2
Na
S-
/~
0
+ 2NaOH
ASSAY OF VOLATILE OILS 373
U.S.P.
Oil of bitter al-
mond ......... 1 Gm. Hydroxylamine Benzaldehyde = 95
Oil of cinnamon .. 10 cc. Sulfite Cinnamic aldehyde = 80
N.F.
Benzaldehyde .... 1 Gm. Phenylhydrazine Benzaldehyde = 85
Carvone, the principal ketone present in the oil, reacts with the
sodium sulfite, forming a water-soluble addition product as
follows:
376 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
()<sE~ ONa
) ~
The presence ,of free alkali in the aqueous layer renders other
components of the oil, such as phenols, water-soluble and also
tends to reverse the addition reaction. To pt:event this the
sodium hydroxide is neutralized by the addition of sodium acid
sulfite:
The difference between the volume of oil used as the sample and
the volume of the oily layer which remains insoluble represents
the carvone which dissolved in the aqueous layer. If drops of
oil adhere to the walls of the fiask,-they may be made to rise into
the neck by gently tapping and rotating it. If the residual
liquid measures 4.5 cc., the percentage of carvone by volume in
the oil would be 10 ~O 4.5 X 100 = 55 per cent.
The only other official oil evaluated for its ketone content is oil
of spearmint. It is assayed in exactly'the same way as is oil of
ASSAY OF VOLATILE OILS 377
O -OCH3
-CH 2-CH CH 2
+KOH~
O-OCH3
-CH2-CH CH2
+HOH
378 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
U.S.P.
Oil of clove, , , , , .. '.' ...... 10 KOH Eugenol C lOH ,2 0 2 = 82
N.F.
Oil of myrcia .............. 10 KOH Phenols = 50 to 60
Oil of pimenta. , .......... 10 KOH Eugenol,C ,o H 120 2 = 65
Oil of thyme ... , .......... 10 KOH Phenols = 20
Exercise 110
Object.-Assayof Oil of Bitter Almond for Hydrocyanic Acid.
Materials Required.--o.75 Gm. of magnesium sulfate.
0.5 N sodium hydroxide.
Potassium chromate indicator (10 Gm. in 100 cc. of water).
0.1 N silver nitrat~.
Procedure.-l. "Dissolve 0.75 Gm. of magnesium sulfate in 45 cc. of
distilled water, add 5 cc. of half-normal sodium hydroxide and 2 drops of
potassium chromate T.S., and titrate the solution with tenth-normal silver
nitrate to the production of a permanent reddish tint."
The magnesium sulfate reacts with the sodium hydroxide,
forming magnesium hydroxide and sodium sulfate:
MgS0 4 + 2NaOH~Mg(OH)2 + Na 2S04
The resulting mixture is titrated with 0.1 N silver nitrate to the
appearance of a permanent end point to correct for the presence
of impurities in the reagents used which would react with the
silver nitrate in the next step of the assay.
2. "Pour this mixture into a 100 cc. flask containing about 1 Gm. of
Oil of Bitter Almond, accurately weighed, mix well, and titrate again with
tenth-normal silver nitrate until a red tint, which does not disappear on
shaking, is reproduced. Conduct this titration as rapidly as possible.
Each cubic centimeter of tenth-normal silver nitrate corresponds to 0.002702
Gm. of HCN."
The freshly precipitated Mg(OH)2 splits up the cyanhydrin
present in the oil and at the same time furnishes a white back-
ground against which the end point of titration may be observed.
The reacti~n may be represented as follows:
H
/
20 -C-OH
"C=N + Mg(OH),-.
H
/
o
C~
2 0 + Mg(CN)2 + 2HOH
380 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Exercise 111
The ascaridol in the oil dissolves in the 60 per cent acetic acid.
The exact nature of the reaction that occurs is not known, but it
may be represented as follows:
o
~
{D I
+ 2CH'COOH~O + 2HOH + 0,
I-O-C-CHs
A A
Any variation in the strength of the acetic acid employed causes
variable amounts of the constituents of the oil (decomposition and
reduction products of ascaridol) to dissolve in the acetic acid;
consequently, the acetic acid solution used must be of exactly
60 per cent strength.
2. "Shake the mixture continuously and vigorously for a period of five
minutes and add sufficient of the acetic acid solution to raise the lower limit
of the oily layer within the grad~ated portion of the neck. When the
liquids have completely separated so that a sharp meniscus is discernible,
note the volume of the oily layer, at 25°0. It measures not more than 4 cc.
and not less than 2 cc., indicating not less than 60 per cent and not more than
80 per cent, by volume, of the acetic-acid soluble fraction of the Oil."
Exercise 112
-
.~'
The acidified calcium chloride solution, when
added to the alcoholic spirit, throws the volatile oil
out of solution and the oil dissolves in the kerosene
FIG. 64.- when the mixture is shaken. The calcium chloride
Babcock bot-
tIe. (Cour- serves to' "salt out" any volatile oil from the diluted
te8Y Fi8her alcoholic mixture. The acid insures the absence of
Scientifio
Company.) alkali which would render acids, traces of aldehydes,
etc., water-soluble. The determination is carried
out in a Babcock bottle (Fig. 64), the neck of which is calibrated
into eight main divisions of 0.2 cc. each.
2. "Centrifuge for five minutes at about 1500 revolutions per minute
and then read the volume of oil in the stem. Subtract 5 divisions for the
ASSAY OF VOLATILE OILS 385
kerosene added and multiply the remaining number of divisions by 4.2 to
obtain the volume of oil of peppermint in 100 cc. of the Spirit."
Amount Official
Spirit used, Factor requirement,
cc. per cent
ALKALOIDAL ASSAYING ..
Proximate Assays.-Alkaloidal assays are commonly referred
to as proximate assays. When such substances as the alkaloids
and glycosides were first isolated from. vegetable matter, they
were regarded as plant principles which still retained their
vegetable character, which entered immediately into the composi-
tion of the plant, and which had not been: altered in composition.
Consequently, they were called proximate principles is opposed
to the ultimate principles, such as water, carbon, acetic acid, and
methyl alcohol which had previously been obtained more ot less
from all plant products by the methods of pyroanalysis (destruc-
tive distillation).
General Principles.-The alkaloidal drugs and preparations
derived from them constitute a relatively large1>roportion of the
official substances which are employed frequently in modern
therapy. As a class of medicinal agents, they ar~ ch~racterized
by their high potency. A slight deficiency of alkaloid in a
preparation may cause a marked decrease in physiological
effect; on the other hand, a slight excess may cause toxic effects
when the preparation is administered. It therefore follows that
the accurate estimation of the quantity of alkaloids present in a
medicinal substance is an important subdivision of pharma-
ceutical analysis.
"The assay of alkaloidal drugs and preparations is generally
performed for purposes of standardization, proof of purity,
commercial evaluation, or pharmaco-Iegal purposes. Methods of
various types have been developed for the quantitative estimation.
of these principles, e.g., gravimetric, volumetric, colorimetric,
potentiometric, and physiological. The official assays are limited
to the gravimetric, volumetric, and physiological methods, only
the first two of which come within the scope of this work.
The amounts of alkaloids which occur in crude drugs are subject
to considerable variation in different samples of the same drug.
386
ALKALOIDAL ASSAYING 387
The variations may be caused by several factors, i.e.: (1) the age
of the plant when it is collected; (2) the season of the year when
the drug is harvested; (3) the soil and climate in which the drug is
grown; (4) the conditions under which the drug is collected,
dried, and stored. The quantity of alkaloid present in galenical
preparations is alscl ,subject to variation due to a number of
factors, some of'--which are: (a) the quality of drug employed;
(b) the menstruum used in the extraction of the alkaloid; (c)
the ltmount of decomposition of the alkaloid during the process
of extraction and during the period of storage.
Many alkaloidal preparations deteriorate comparatively
rapidly, the rate of deterioration being markedly affected by the
nature of the alkaloid, the pH value of the preparation, heat, and
light. Frequent restandardization of the alkaloidal drugs and
their preparations is therefore essential.
In view of the fact that the alkaloids may comprise only a frac-
tion of 1 per cent of the substance assayed and that this small
amount must be separated from numerous other constituents
present in the crude drug or preparation, such as resins, volatile
and fatty oils, coloring matter, glycosides, fatty acids, gums, and
proteins, it is evident tnll1t the exact technique involved in any
given method must be carefully adhered to in order to estimate
the variations in alkaloidal content. It is this special technique
that characterizes the chemicai assay of alkaloidal drugs rather
than the gravimetric or volumetric nature of the procedure
employed.
The principles employed in the quantitative determination of
the alkaloids by chemical methods are based upon certain
characteristic properties of these substances. The following
general properties are possessed by most of the members of this
class of compounds: (1) Alkaloids are usually sparingly soluble
in water but readily soluble in certain organic solvents which are
immiscible with water, such as chloroform, ether, amyl alcohol,
benzene, petroleum benzin, or mixtures of these solvents. (2)
Alkaloids combine directly with acids to form salts which are
usually soluble in water but insoluble in certain organic solvents
such as chloroform and ether. (3) Alkaloids are liberated and
usually precipitated from aqueous solutions of their salts by
alkalies. (4) Alkaloids form highly insoluble precipitates with a
388 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
pH range
Salt of Average for Indicator
pH
indicator
·
-~ ~
f--05
in the organic solvent as described under A.
C. By Continuous Extraction.-An accurately
1-
i weighed portion of the ground drug is placed in
i an extraction thimble and the thimble trans-
I ferred to a suitable extractor (a Soxhlet extractor
oil
~ : I
of appropriate size is satisfactory). The drug is
! i moistened with the specified solvent and mixed
1 !
:
2:
~1
~18~
by means of a stirring rod and allowed to stand
about 5 min. It is then made alkaline with
~ the specified quantity of ammonia T.S. and
-'--. \. ,I.~" thoroughly mixed.
~ .7;. 10
The stirring rod is rinsed
with a small portion of th~ solvent and the drug
- r... :. macerated for from 6 to 12 hr. or over night.
Le. The drug is covered wi~h a pledget of purified
FIG. 66.-Per- cotton and packed in the thimble, a sufficient
cola tor recom- quantity of solvent is added and the drug
mended for type
process B (meas- extracted for a specified period of time. The
urements are given solvent remaining in the extraction chamber is
in millimeters).
transferred to the receiving flask and the liquid
extract treated for the extraction of alkaloids.
An extraction apparatus of the type illustrated in Fig. 60
and described on page 337 is very satisfactory. The continuous
extraction process requires a small amount of the organic solvent
and, in most cases; complete extraction of the alkaloids is obtained
in from 3 to 5 hr.
4. Extraction of the Alkaloids from Organic Solvents with Acid.-
The alkaloids are extracted from ethtlreal or chloroformic
solutions by shaking with dilute acids. The concentration and
quantity of the acid employed are left to the discretion of the
analyst, but the use of 10 cc. of a normal or 5 per cent acid or
sufficient to render the mixture distinctly acid for the first extrac-
ALKALOIDAL ASSAYING 399
tion and of 10 cc. portions of 0.5 N or 2 per cent acid for succeed-
ing extractions will be found to be practical and convenient. The
shaking of the immiscible solvents should not be violent, but it
should be sufficient to mix them thoroughly without emulsifica-
tion. Repeated successive extractions with small portions of the
acid must be continued until the alkaloid is completely removed
from the ethereal or chloroformic liquid as shown by tests with
the designated reagents. Each portion of the acid solution
should be carefully separated from the organic solvent and run
directly into another separatoryfunnel. In all assays, the extrac-
tion should be continued until 0.5 cc. of the last acid washing
shows no turbidity on the addition of a drop of mercuric
potassium iodide T.S., or, in the case of caffeine and colchicine,
on the addition of a drop of iodine T.S. If traces of organic
solvent are drawn off with the acid solution, they may be
removed by washing the combined acid extractives with 2 to 3
cc. of ether or chloroform which is separated and washed in turn
with about 5 cc. of distilled water, the aqueous washings being
separated and added to the acid solution.
If sulfuric acid is used, the acid converts the free alkaloids dis-
solved in the organic solvent into their sulfates which pass into
solution in the aqueous acid layer of the immiscible solvents when
the mixture is shaken, leaving chlorophyll, resins, fixed and
volatile oils, and other impuritIes dissolved in the organic solvent.
The rate at which the alkaloids pass from solution in the organic
solvent into the acid solution is increased greatly by shaking the
mixture, since a greater area of contact surface between the
liquids is produced. Sulfuric acid solution is employed to extract
the alkaloids, because the ammonium sulfate formed in the next
step in the procedure is not appreciably solub~e in the organic
solvent used for the final extraction of the alkaloid.
5. Extraction of the Alkaloids from Acid Solution with Organic
Solvents.-The acid solution of the alkaloids contained in a
separatory funnel is made alkaline, in most cases with ammonia
T.S., and then shaken with several successive portions of organic
solvent, such as ether, chloroform or ether-chloroform mixture.
The volume of organic solvent used in each extraction should be
at least one-half that of the aque<;ms solution. The extraction
with portions of organic solvent must be repeated as long as any
400 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Exercise 114
The alkaloids found in the rhizomes and roots (If hydrastis con-
sist chiefly of hydrastine and berberine in varying proportion.
The latter is almost inactive, while the hydrastine is very active
physiologically. Consequently, a determination of the total
alkaloids of hydrastis would not ~be a correct measure of the
therapeutic activity of the drug. Ether is used, therefore, as the
organic solvent in the extraction of the alkaloids, because hydras-
tine is readily soluble and berberine is practically insoluble in this
solvent. The aliquot portion of 50 cc. of the ethereal solution is
equivalent to 59100 X weight in grams of the sample of hydrastis.
403
404 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Exercise 115
Object.-Assay of Cinchona for Total Alkaloids.
Materials Required.-5 Gm. of cincona in No. 60 powder.
200 cc. of ether-chloroform mixture.
100 cc. of chloroform.
Procedure.-l. "Place 5 Gm. of Cinchona, in fine powder, and 15 cc. of
3 per cent hydrochloric acid in a 500-cc. flask and heat the mixture on a
water bath for one hour. Cool and add 200 cc. of ether-chloroformic solu-
tion (ether, 3 volumes, chloroform, 1 volume) and 10 cc. of stronger ammonia
T.S. Stopper the flask tightly and shake it for one hour in a mechanical
shaker. Allow the mixture to stand over night, again shake it for one-half
hour, and then allow the drug to settle. (If the supernatant liquid is not
clear, add a few cc. of distilled water, again shake the contents of the flask
vigorously, and allow the drug to settle.)" (See General Procedure 3A,
page 395.)
Cinchona bark contains about 20 alkaloids the most important
of which are quinine, quinidine, cinchonine, and cinchonidine.
The alkaloids occur as salts in combination with quinic and cin-
chotannic acids. These salts are decomposed when boiled with
hydrochloric acid with the formation of the corresponding
alkaloidal hydrochlorides which are soluble in the water. When
the aqueous solution is made alkaline with ammonia, the liberated
alkaloids pass into solution in the ether-chloroform mixture
almost completely, due to the large volume of the latter
employed.
2. "Quickly decant 160 cc. of the clear, ether-chloroformic solution, meas-
ured at approximately the same temperature as the original ether=chloro-
formic solution and representing 4 Gm. of drug." (See General Procedure 3,
page 395.)
The aliquot portion is equivalent to 16%00 X the weight of
the sample taken.
3. "Transfer the solution to a separator, rinse the measuring vessel with
a small quantity of the original menstruum and add the rinsings to the
separator. Completely extract the alkaloids with approximately 5 per cent
sulfuric acid and collect the acid solution of tIle alkaloids'in a second separa-
tor." (See General Procedure 4, page 398.)
4. "Make the acid solution strongly alkaline with ammonia T.S. and
completely extract the alkaloids with chloroform. Evaporate or distil the
chloroform in a tared beaker or flask and dry the alkaloidal residue to con-
stant weight at 100°C. The weight obtained, multiplied by 25, represents
the per cent of the alkaloids of cinchona in the drug." (See General Pro-
cedures 5, 6, and 7, page 399.)
The ammonia water reacts with the alkaloidal sulfates,
setting the alkaloids free and forming ammonium sulfate.
Only a slight excess of ammonia should be used to make t~e
solution alkaline, since the cinchona alkaloids are appreciably
soluble in strong ammonia solution. The alkaloids set free by
the alkali dissolve in the chloroforI,n.
It has been reported that the cinchona alkaloids form addition
products with chloroform which are not entirely broken down
when the residue from the chloroformic solution of the alkaloids
is dried at 100°C. The error in the assay results caused by the
retention of chloroform by the alkaloidal residue when the latter
is dried as directed, however, is negligible.
The gravimetric method is employed in the determination
of the alkaloids in the residue, because the indicator end point
is not sharp when the mixture of alkaloids is titrated.
The U.S.P. requires that cinchona contain not, less than 5 per
cent total alkaloids when assayed by the above method. Calcu-
late the percentage of alkaloids found in the sample assayed
and compare the results with the official requirement.
Questions and Problems
1. Why is hydrochloric acid used in the initial menstruum to extract the
alkaloids from cinchona?
2. Does the ether-chloroform mixture extract practically all of the alkaloid
present in the sample in the first step?
3. Why should the addition of a large excess of ammonia to the acid
solution of the alkaJoids previous to the shaking out with chloroform be
avoided?
Exercise 116
Object.-Assay of Compound Tincture of Cinchona.
Materials Required.-50 cc. of compound tincture of cinchona.
200 cc. of chloroform.
200 cc. of ether.
Procedure.-l. "Accurately measure 50 cc. of Compound Tincture of
Cinchona and evaporate it, at a temperature not exceeding 100°C., to a
OFFICIAL TYPE METHODS 407
volume of about 10 cc. Add sufficient asbestos fiber or paper pulp to
adsorb the liquid, and continue the evaporation to dryness. Transfer the
residue to a flask or bottle, add 200 cc., accurately measured, at room tem-
perature, of ether-chloroform mixture (ether 4 volumes, chloroform 1 vol-
ume) and sufficient ammonia T.S. (which may be used to rinse out the
adhering portions of the Tincture from the evaporating dish) to render the
mixture strongly alkaline. Securely stopper the container and shake it
mechanically during one hour, or intermittently during two hours, and then
allow the mixt,ure to stand over night."
The tincture is evaporated to drive off the alcohol which is
miscible with ether and chloroform. An adsorbent such as
asbestos fiber or paper pulp (filter paper torn into small pieces)
is added so that the non-volatile residual matter consisting
largely of alkaloidal hydrochlorides, glycerin, and cinchona
red will be deposited as a thin film when the tincture is evapo-
rated. If some adsorbent is not used, a resinous, varnish-like
residue usually results from which the alkaloids cannot be
extracted readily. The addition of ammonia T.S. liberates the
alkaloids which dissolve in the ether-chloroform mixture along
with the glycerin, cinchona red, and considerable other extractive
matter.
2. "Again shake the mixture intermittently for half an hour, allow it to
settle, quickly decant 160 cc. (representing 40 cc. of the Tincture) of the
approximately clear liquid. Filter this into a separator and wash the
measuring vessel with sufficient of the ether-chloroform mixture, adding
the rinsings to the filter. Extract the alkaloids from the clear liquid with
acidulated water, using sufficient dilute sulfuric acid to render the contents
of the separator and each extract distinctly acid to litmus paper. Pass the
acid extracts in succession through a wetted, double filter into a second
separator. Render the combined liquids distinctly alkaline ,with stronger
ammonia T.S., and extract with chloroform. Pass the chloroformic
extracts through a double filter, which is kept saturated with chloroform,
into a suitable, tared receptacle. Evaporate the chloroform on a water
bath, dry the residue to constant weight at 100°C., and weigh. The weight
multiplied by 2.5 indicates the weight of alkaloids in 100 cc. of the Com-
pound Tincture of Cinchona." (See Assay of Cinchona, Procedures 2, 3,
and 4, page 405 for explanation.) "
Volumetric Assays by the Aliquot-part Method
Exercise 117
Object.-Assay of Ipecac for Ether-soluble Alkaloids.
Materials Required.-lO Gm. of ipecac in No. 60 powder.
200 cc. of ether.
408 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
The ammonia sets the emetine and cephaeline free, and the
liberated alkaloids dissolve in the ether.
The residue consists almost entirely of emetine and cephaeline
which dissolve in the standard acid solution, forming emetine
and cephaeline sulfates, as illustrated by the following reaction
for emetine:
2C16H2202N + H2S0C~(C15H2202N)2.H2S04
Each cubic centimeter of 0.1 N H 2 S0 4 consumed corresponds to
0.024 Gm. of the ether-soluble alkaloids of ipecac.
The Pharmacopoeia requires that ipecac contain not less than
1.75 per cent of ether-soluble alkaloids. Calculate the percentage
of ether-soluble alkaloids contained, in the sample assayed and
compare the results with the official requirement.
Fluidextract of Ipecac, U.S.P., and Tincture of Ipecac, N.F., are
assayed for total ether-soluble alkaloids by procedures which
involve the same principles as the assay of ipecac.
Questions and Problems
1. Why is ipecac assayed for its content of ether-soluble alkaloids?
2. Ascertain the molecular weights of emetine and cephaeline from the
table, U.S.P. page 587, and show how the alkaloidal equivalent of each
cubic centimeter of 0.1 N H 2S0 4 is derived.
8. Would the error in the assay result be very considerable if the ether-
soluble alkaloids of the ipecac consisted almost entirely of emetine?
4. Enumerate several possible sources of error which might be encountered
in the assay of ipecac.
Exercise 118
Object.-Assay of Areca.
Materials Required.-15 Gm. of a'teca.
250 cc. of ether.
15 of a saturated solution of sodium bicarbonate (about 1 in 10).
About 3 Gm. of sodium bicarbonate.
Procedure.-l. "Place 15 Gm. of Areca, in moderately fine powde!' and
accurately weighed, into a suitable flask, add 150 cc. of ether, allow to stand
about five minutes, then add 15 ce. of a saturated solution of sodium bicar-
410 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
bonate. Agitate the mixture in a mechanical shaker for one hour, or inter-
mittently during two hours, set it aside overnight, and again agitate in a
mechanical shaker for one hour. Separate 100 cc. of the clear ethereal
liquid." (See General Procedure 3A, page 395.)
Amount
Official
used, Assayed
Substance requirement,
Gm. for
per cent
or cc.
U.S.P.
Cinchona ............... 5 Total alkaloids (n.l.t.) 5
Cinchona, compound tinc-
ture of ............... 50 Total alkaloids 0.4 to O.5W jV
Ipecac ................. 10 Ether-soluble (n.Lt.) 2
alkaloids
Ipecac, fluidextract of. ... 10 Ether-soluble 1. 8 to 2. 2W jV
alkaloids
N.F.
Areca .................. 15 Arecoline (n.l.t.) 0.2
Hy\lrastis ............... 10 Ether-soluble (n.l.t.) 2.5
alkaloids
Hydrastis, extract of ..... 2* Ether-soluble 9 to 11
alkaloids
Hydrastis, fluidextract of 5* Ether-soluble 2.25 to 2. 75W jV
alkaloids
Hydrastis, tincture of .... 25* Ether-soluble 0.45 to 0.55WjV
alkaloids
Ipecac, tincture of ....... 50* Ether-soluble 0.18 to 0.22W jV
alkaloids
drug with a mixture of 8 cc. of stronger ammonia T.S., 10 cc. of alcohol and
20 cc. of ether, and mix thoroughly. Macerate the mixture over night, then
extract it for not less than three hours on a water bath, using 'ether as the
solvent. The following alternative process may be used: Moisten 25 Gm.
of Hyoscyamus, in fine powder, with a mixture of 8 cc. of stronger ammonia
T.S., 20 cc. of ether and 10 cc. of chloroform, in a small Ilercolator, previously
prepared by packing the outlet with a pledget of purified cotton. Macerate
the mixture over night, paek it in the percolator and extract by slowly per-
colating with a mixture of 3 parts of ether and 1 part of chloroform, by
volume. Continue the percolation until the 3 or 4 cc. of percolate last
passed, when evaporated to dryness and the residue dissolved in dilute
sulfuric acid, fails to become turbid when treated with mercuric potassium
iodide T.S." (See General Procedure 3B and C, page 397.)
The alkaloids are set free by the ammonia water and dissolve
in the chloroform.
4. "Evaporate or distil the chloroform from the combined extractions
until reduced to a small volume, then evaporate to dryness on a water bath,
and keep at this temperature for fifteen minutes. Dissolve the residue in
chloroform, evaporate to dryness on a water bath, and continue the heating
for fifteen minutes. Repeat this treatment for the third time."
The solution of the alkaloids in organic solvent is evaporated
to drive off the solvent and ammonia. The residue is repeatedly
dissolved, evaporated, and dri,ed to drive off small amounts of
volatile amines which are basic and, unless removed, would
neutralize some of the acid in the next step of the procedure with
subsequent high results.
5. "Dissolve the resulting residue in ch\oroform, add 15 cc. of fiftieth-
normal sulfuric acid, remove the chloroform by evaporation, and titrate the
excess acid with fiftieth-normal sodium hydroxide, using methyl red as the
indicator. Each cubic centimeter of fiftieth-normal acid is equivalent to
0.00578 Gm. of the alkaloids of Hyoscyamus."
The residual alkaloids, ~hich consist chiefly of the isomers
atropine and hyoscyamine, react with some of the 'sulfuric
acid as follows:
2C 17H 23 0 3N + H2S04~(C17H2303N2).H2S04
289.3 98
Since 98 Gm. of H 2S0 4 is equivalent to 2 X 289.19 Gm. of
atropine or hyoscyamine, each cubic centimeter of 0.1 N H 2S0 4
414 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Exercise 121
Amount
Official
used,
Substance requirement,
Gm.or
per cent
cc.
U.S.P.
Belladonna leaf ................... . 10 (n.l.t.) l3
Belladonna ointment .............. . 25 O. 118 0 O. 132
Belladonna, pilular extract of ...... . 3 1.18 to 1.32
Belladonna plaster ................ . 10 0.25 to 0.30
Belladonna, powdered extract of ... . 2 1.18 to 1.32
Belladonna root ................... . 10 (n.l. t.) 0.45
Belladonna root, fluidextract of .... . 10 0.405 to 0.495WjV
Belladonna, tincture of ............ . 100 0.027 to 0.033WjV
Hyoscyamus ...................... . 25 (n.l.t.) 0.040
Hyoscyamus, pilular extract of ..... . 5 0.135 to 0.175
Hyoscyamus, powdered extract of .. . 5 0.135 to 0.175
Hyoscyamus, tincture of ........... . 250 0.0034 to 0.0046WjV
Stramonium ....... '............... . 10 (n.l.t.) 0.30
Stramonium, pilular extract of ..... . 3 1.10 to 1.30
Stramonium, powdered extract of ...' 2 1.10 to 1.30
Stramonium, tincture of ........... . 100 0.027 to 0.033WjV
N.F.
Belladonna leaf, fluidextract of ..... . 10 0.27 toO.33W/V
Hyoscyamus, fluidextract of . ...... . 25 0.035 to 0.045WjV
Stramonium, fluidextract of ........ . 10 0.25 to 0.35WjV
and, after shaking the mixture, add 1 Gm. of ammonium chloride. Stopper
the flask, shake it frequently during ten minutes and set it aside in a cool
place over night. Remove the stopper and brush any adhering crystals back
into the flask."
4. "Decant the ethereal layer through a small filter p~l'V.' ~~nse the
flask and contents with 15 cc. of ether and pass these washings through
the filter, and again wash the filter with an additional small quantity of
ether. When all of the ether has passed through the filter, pour the aqueous
layer upon the filter without trying to remove the crystals from the flask.
Wash the crystals in the flask and the contents of the filter with distilled
water, previously saturated with morphine, until the washings are colorless.
Then add a few drops of distilled water to displace the morphinated water."
U.S.P.
Opium ............. , .... 6 0.02852 9.5
Opium, granulated ...... " 6 0.02852 10 to 10.5
Opium, powdered ......... 6 0.02852 10 to 10.5
Opium, tincture of ........ 60 0.02852 0.95 to 1.05W/V
Opium, tincture of, cam-
phorated .............. 100 0.00570* 0.035 to 0.0045
N.F. .....
Opium, extract ...... , .... 4 0.02852 19.~ to 20.5
Exercise 123
4. "To this weighed residue in the flask, add 5 cc. of tenth-normal sulfuric
acid, 5 cc. of distilled water, and a few drops of chloroform, and heat the
mixture at 70°C. for ten minutes. Filter the liquid through a pledget of
purified cotton, wash the flask and cotton with distilled water, reject the
filtrate and washings, and remove as much of the water from the cotton as
possible. Dissolve the residue, if any, which may remain on the cotton by
washing it first with a little alcohol and then with ether; collect the alcohol-
ether washings in the flask, evaporate, and dry the residue to constant
weight at 100°C. Deduct this weight from the weight of residue previously
obtained. The difference is the weight of colchicine obtained from 5 Gm.
of CoI<:hicum Seed."
U.S.P.
Colchicum seed ............ 15 Gm. 5 Gm. 0.45
Colchicum seed, tincture of 150 cc. 50 cc. 0.036 to 0.044W IV
N.F.
Colchicum corm ........... 15 Gm. 5Gm. 0.35
Colchicum corm, fluidex-
tract of. ................ 15 cc. 5 cc. 0.31 to 0.39WIV
Colchicum corm, strong
tincture of .............. 45 cc. 15 cc. 0.125 to 0.155WIV
Colchicum seed, fluidextract
of ..................... 15 cc. 5 cc. 0.4 toO.5WIV
Exercise 124
hour. Now allow the mixture to stand for twelve hours or over night in a
cool place, At the expiration of this period, shake the container gep.tly for
fifteen minutes, and then allow the liquids to separate."
dissipated. Cool to room temperature and titrate the excess of acid with
fiftieth-normal sodium hydroxide, using 1 drop of methyl red T:S. as the
indicator. Each cubic centimeter of tenth-normal sulfuric acid is equivalent
to 0.03342 Gm. of strychnine."
Amount
used, Official'requirement,
Substance
Gm. or per cent
cc.
U.S.P.
Nux vomica ................ '.. . 15 Strychnine = (n.Lt.) 1.15
Nux vomica, extract 9f. ....... . 1.5 Strychnine = 7 to 7.75
Nux vomica, tincture of ....... . 100 Strychnine = 0.108 to 0.120
N.F.
Nux vomica, fluidextract of ..... 10 Strychnine = 1.05 to 1.25
Object.-Assay of Guarana.
Materials Required.~ Gm. of guarana in No. 60 powder.
250 cc. of chloroform.
Procedure.-l. "Place 6 Gm. of Guarana, in fine powder and accurately
weighed, into a suitable container, add 120 cc. of chloroform, allow the
mixture to stand about five minutes, and then add 6 cc. of ammonia water
and 6 cc. of distilled water. Shake t.he mixture continuously for one hour
or intermittently dUring two hours, and allow it to stand overnight.
Again shake intermittently during one half hour and separate 100 cc. of
the clear chloroformic solution."
small portions of distilled water until no test for alkaloid is obtained with
iodine T.S. in a portion (1 cc.) of the filtrate after a:cidulating strongly with
diluted sulfuric acid."
Amount
used, Official requirement,
Substance
Gm. or per cent caffeine
cc.
N.F.
Guarana ................. . 6 4.0
Guarana, fluidextract of ... . 5 3.6 to 4.4 W IV
Kola ................... . 12 1.0
Kola, fluidextract of ....... . 10 0.85 to 1.15W IV
Exercise 126
weighed, in 10 cc. of warm distilled water, and titrate the solution with
normal hydrochloric acid, using phenolphthalein T.S. as the indicator: not
more than 5.5 cc. of normal hydrochloric acid is required to neutralize 2 Gm.
of the dried Theobromine with Sodium Salicylate."
Exercise 129
Exercise 130
Object.-Assay of Ephedrine Sulfate.
Materials Required.-O.5 Gm. of ephedrine sulfate.
100 cc. of ether.
10 cc. of alcohol (neutralized to bromthymol blue).
Procedure.-l. "Transfer about 0.5 Gm. of Ephedrine Sulfate, dried over
sulfuric acid for twenty-four hours and accurately weighed, to a separator;
add 10 cc. of distilled water and 5 cc. of ammonia T.S., and extract with six
portions of ether, using 25 ce., 20 ee., 15 ec., 15 ee., 15 cc., and 15 cc.,
respectively."
The ephedrine liberated from the sulfate by the ammonia is
extracted by the ether. Chloroform cannot be used to shake out
the ephedrine because this alkaloid is a sufficiently strong base to
decompose the chloroform and form ephedrine hydrochloride
especially in warm solution. (See test for identity of ephedrine,
U.S.P., page 144.)
2. "Collect the extracts in a beaker, evaporate the ether on a water bath
to about 5 cc., add 10 cc. of alcohol, previously neutralized to bromthymol
blue T.S. with tenth-normal sodium hydroxide, and add from a burette an
excess of tenth-normal hydrochloric acid. Titrate the excess of acid with
tenth-normal sodium hydroxide, using bromthymol blue T.S. as the indi-
cator. The ephedrine thus found is not less than 75.5 and not more than
77.3 per cent of the weight of Ephedrine Sulfate taken. One cubic centi-
meter of tenth-normal hydrochloric acid is equivalent to 0.01651 Gm. of
ephedrine.' ,
Amount
Substance used, Official requirement, per cent
Gm. or
cc.
U.S.P.
Caffeine, citra ted ............... . 1 Anhydrous caffeine = 48 to 52
Caffeine with Bodium benzoate .. . . 1 Anhydrous caffeine = 47 to 50
Codeine phosphate ............. . 0.5 Anhydrous codeine = (n.l.t.) 70
Ephedrine ..................... . 0.5 Ephedrine = 98 to 100
Ephedrine hydrochloride ........ . 0.5 Anhydrous ephedrine = 80 to 82.5
Ephedrine Bulfate . ... " ......... . 0.5 Anhydrous ephedrine - '(:5.5 to 77.3
Ethylhydrocupreine hydrochloride 0.5 Ethylhydrocupreine = (n.l. t.) 90
Eucaine hydrochloride .......... . 0.5 Eucaine hydrochloride = (n.l.t.) 99
Phenacaine hydrochloride ....... . 0.5 Phenacaine = 87.5 to 90.5
Quinine and urea hydrochloride . . . 0.5 Anhydrous quinine = 58 to 65
Theobromine with sodium salicy-
late ......................... . 2 Theobromine = (n.l.t.) 46.5
Theophylline with ethylene dia-
mine ........................ . 2 Anhydrous, theophylline = 70 to 80
Theophylline with sodium acetate. 1 Anhydrous theophylline = 55 to 65
N.F.
Apomorphine hydrochloride, tab-
lete of ...................••... 0.00· Apomorphine hydrochloride = 91 to 109'
Atropine sulfate, tahlets of
containing 0.02 or more Gm .••. 0.08· Atropine sulfate .. 92.5 to 107. 5b
containing 0.0012 to 0.02 Gm .. 0.08· Atropine sulfate .. 91 to 109b
containing less than 0.0012 Gm. 0.08· Atropine sulfate .. 88 to 112'
Caffeine citrated, tablete of ...... . 0.5· Caffeine, citra ted = 43 to 53 b
Caffeine with sodium benzoate,
ampule of. .................. . 0.5· Anhydrous caffeive = 45 to 52b
Caffeine with sodium benzoate,
tablete of. ................... . 0.5· Anhydrous caffeine = 43.5 to 53. 5b
Cocaine hydrochloride, tablets of .. 0.06· Cocaine hyprochloride = 91 to 109b
Codeine phosphate, tablets of. .... 0.06· Anhydrous codeive = 63 to 77'
Codeine sulfate, tablets of. ....•.. 0.06· Codeine sulfate = 91 to 109/>
Emetine hydrochloride, ampuls of 0.3· Emetine hydrochloride = 84 to 92 b
Ephedrine hydrochloride, tablets of 0.06· Ephedrine hydroohl6ride = 91 to 109'
Ephedrine sulfate, ampul. of ..... . 0.5· Ephedrine = 72.6 to 80. 2b
Ephedrine sulfate, solution of. ... . 10 Ephedrine sulfate = 2.8 to 3. 2W IV
Morphine sulfate. tablets of ...... . 0.13· Morphine sulfate = 92.5 to 107. 5b
Morphine and atropine sulfates,
tablets of. ..................•. 0.13· Morphine sulfate = 91 to 109b
Nux vomica alkaloids, solution of . . 20 Strychnine sulfate = 1. 5 to 1.7 W IV
Brucine sulfate = 1. 5 to 1. 7 W IV
Procaine hydrochloride, ampuls of 0.2· Procaine hydrochloride = 95 to 105b •
Procaine hydrochloride, solution of 10 Procaine hydrochloride = 1.9 to 2.1 W IV
Procaine hydrochloride, tablets of. 0.2· Procaine hydrochloride = 92.5 to 107.5'
Quinine dihydrochloride, ampuls of 0.5· Quinine dihydrochloride = 95 to 105b
Quinine hydrochloride and ethyl
carbamate, ampule of . ........ . 0.5· Quinine hydrochloride = 92.5 to 107. 5 b
Quinine and urea hydrochlorides,
ampuls of. ...............••.. 0.5· Quinine and urea hydrochlorides = 54.8 to
63.7·
Quinine phosphate. . ........... . 0.5 Anhydrous quinine = 74 to 78
Quinine sulfate, tablets of ...... . 0.13· Quinine sulfate = 91 to 109b
Scopolamine hydrobromide, tablets
of. .....................••. 0.06·
containing 0.0012 Gm. or more. Scopolamine hydrobromide = 91 to 109b
containing less than 0.0012 Gm Scopolamine hydrobromide = 88 to 112 b
Strychnine nitrate, tablets of .... . 0.13·
containing O. 02 Gm. or more .. . Strychnine nitrate = 92.5 to 107. 5b
containin,,; 0.0012 to 0.02 Gm. Strychnine nitrate = 91 to 109b
containing less than O. 0012 Gm. Strychnine nitrate = 88 to 112b
Strychnine phosphate .......•.... 0.4 Strychnine = 70 to 73
Strychnine sulfate, tablets of .... . 0.13·
containing 0.02 Gm. or more .. . Strychnine sulfate = 92.5 to 107. 5b
containing O. 0012 to O. 02 Gm .. Strychnine sulfate = 91 to 109b
containing less than O. 0012 Gm. Strychnine sulfate = 88 to 112 b
(n.l.t.) = not less than .
• Amount of equivalent sought.
b Per cent of the labeled amount.
CHAPTER XXVII
Exercise 132
The filicic acid and filicin are liberated from their barium salts
and dissolved in the ether, leaving barium chloride in the aqueous
solution.
3. "Filter the combined ethereal solutions, wash the filter with ether,
evaporate, and dry the residue to constant weight at 100°C. This residue
is calculated as crude filicin and its weight should be not less than 24 per
cent of the weight of Oleoresin taken for the assay."
Exercise 133
Object.-Assay of Jalap.
Materials Required.-lO Gm. of jalap in No. 60 powder_
20 cc. of 1 per cent hydrochloric acid.
90 cc. of chloroform.
120 cc. of alcohol.
Procedure.-l. Place 10 Gm. of jalap, in fine powder and accurately
weighed, with about 60 cc. of a mixture of 9 volumes of alcohol and 1 volume
of water, in a flask provided with a reflux tube or condenser, and digest the
mixture on a steam bath during Y2 hr. Transfer the warm mixture to a
small-percolator, allow it to drain, press the marc down gently, and percolate
with the warm alcohol-water mixture until 100 cc. of percolate, when cooled,
is obtained, and mix thoroughly.
Amount
used,
Substance Official requirement, per cent
Gm. or
cc.
U.S.P.
Aspidium ........................... . 125 Crude filicin = 1.5
Aspidium, oleoresin of ................ . 3 Crude filicin = 24
Cantharides. . . . . . . . . . . . . . . . .. ... . .. 15 Cantharidin = 0.6
Podophyllum ................. . 10 Resin = ~
Soluble barbital. ............. . 1 Barbital = 88 to 90
Soluble phenobarbital. .. 0.5 Phenobarbital = 90.4 to 91.4
N.F.
Acetophenetidin, tablets of. .......... . 0.3· Acetophenetidin 1= 92.5 to 107. 5b
Acetophenetidin and phenyl salicylate,
tablets of. .. .. . . . . .. . ........ .
Aminopyrine, elixir of . ......... . 5 Aminopyrine = 3.7 to 4.3W/V
Aminopyrine, tablets of. . . .. . .. I" Aminopyrine = 92.5 to 107. 5b
Barbi tal, elixir of. . . .. ...... . 10 Barbital = 3.2 to 3.8W/V
Barbital, tablets of, more than 0.07 Gm .. 0.3" Barbital = 92.5 to 107. 5 b
0.07 Gm. orle8s .......... . 0.3· Barbital = 91 to 109b
Ipomoea .................. . 10 Total resins = 15
Jalap...... . . . . . . . . . . . . . . . . . . 10 Total resins = 9
Jalap, fluidextract of. .. . . ... .. 2 Resin = 8.5 to 9.5WIV
Jalap, tincture of ...... , ... . 10 Resin = 1. 7 to 1. 9W IV
Phenobarbital, elixir of ........ . 25 Phenobarbital = 0.38 to 0.42W/V
Phenobarbital, tablets of
more than 0.07 Gm .. : .......... . 0.3· Phenobarbital = 92.5 to 107. 5 b
0.07 Gm. or less .... 0.3· Phenobarbital = 91 to 109b
Soluble barbital, tablets of
more than 0.07 Gm ............... . 0.3· Barbital = 92.54,0 107. Sb-
0.07 Gm. or less .................. . 0.3· Barbital = 91 to 109 b
Soluble phenobarbital, tablets of
more than 0.07 Gm ... 0.3 a Phenobarbital = 92.5 to 107. 5b
0.07 Gm. orless ... 0.3 a Phenobarbital = 91 to 109b
I
and wash the cotton with small portions of the solvent. Evaporate the
combined filtrate and washings on a water bath with the aid of a current of
air, and dry the residue of phenobarbital to constant weight at a temperature
not exceeding 100°C."
Exercise 135
Object.-Assay of P~psin.
Exercise 136
Object.-Assay of Pancreatin for Starch Digestive Power.
Materials Required.-5 Gm. of powdered potato starch.
0.3 Gm. of pancreatin.
0.2 cc. of 0.1 N iodine solution.
Procedure.-l. "Determine the percentage of moisture in potato starch
by drying about 0.5 Gm., accurately weighed, at 120°0., for four hours.
Thoroughly mix a quantity of the starch, equivalent to 3.75 Gm. of dry
starch, with 10 cc. of cold distilled water. Add the mixture with constant
stirring to 75 cc. of distilled water, previously heated to from ,50° to 60°0.,
contained in a tared, 250-cc. beaker. Rinse the remaining starch into the
beaker with 10 ee. of distilled water, heat the mixture to boiling, and boil it
gently, with constant stirring, for five minutes, or until a translucent, uni-
form paste is obtained."
448 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Exercise 137
Object.-Assay of Pancreatin for Casein Dige'stive Power.
Materials Required.-D.l Gm. of casein.
1 cc. of 0.1 N sodium hydroxide.
01. Gm. of pancreatin.
1 cc. of glacial acetic acid.
10 cc. of alcohol.
Procedure.-1. "Place O:I'Gm. of finely powdered casein in a 50 cc. volu-
metric flask, add 30 cc. of distilled water, and shake well to bring the casein
into suspension. Add exactly 1 cc. of tenth-normal sodium hydroxide, and
heat the mixture at 40°C. until the casein is completely dissolved, which
should not require more than thirty minutes. Cool, add sufficient distilled
'water to make 50 cc., and mix well."
Immediately immerse the test tube in a water bath at 40°0., and 'keep it
at this temperature for one hour. Then remove from the bath, and add 3
drops of the acetic acid mixture. No precipitate is produced."
Exercise 138
Object.-Assay of Rennin.
Materials Required.--o.l Gm. of rennin.
0.1 Gm. N.F. reference rennin (a carefully preserved, stable, powdered
rennin that has been repeatedly tested for a number of years so that its
stability and its standard are definitely established. It coagulates approxi-
mately but not less than 25,000 times its weight of fresh cow's milk).
100 cc. of cow's milk.
ASSAY OF ENZYME-CONTAINING SUBSTANCES 451
Proportional parts
Natural 0 1 2 3 4 5 6 7 8 9
numbers
11213141516171819
10 0000 0043 0086 0128 0170 0212 0253 0294 0334 0374 4 8 12 17 21 25 29 3337
11 0414 0453 0492 0531 0569 0607 0645 0682 0719 0755 4 811 15 19 23 26 30 34
12 0792 0828 0864 0899 0934 0969 1004 1038 1072 1106 3 7 10 14 17 21 24 2831
13 1139 1173 1206 1239 1271 1303 1335 1367 1399 1430 3 6 10 13 16 19 23 2629
14 1461 1492 1523 1553 1584 1614 1644 167a 1703 1732 3 6 912 15 1821 24 27
15 1761 1790 1818 1847 1875 1903 1931 1959 1987 2014 3 6 811 1417 20 2225
16 2041 2068 2095 2122 2148 2175 2201 2227 2253 2279 3 5 811 1316 1821 24
17 2304 2330 2355 2380 2405 2430 2455 2480 2504 2529 2 5 710 1215 1720 22
18 2553 2577 2601 2625 2648 2672 2695 2718 2742 2765 2 5 7 9 1214 1619 21
19 2788 2810 2833 2856 2878 2900 2923 2940 2967 2989 2 4 7 9 1113 1618 20
20 3010 3032 3054 3075 3096 3118 3139 3160 3181 3201 2 4 6 811 1315 1719
21 3222 3243 3263 3284 3304 3324 3345 3365 3385 3404 2 4 6 810 1214 1618
22 3424 3444 3464 3483 3502 3522 3541 3560 3579 3598 2 4 6 810 1214 1517
23 3617 3636 3655 3674 3692 3711 3729 3747 3766 3784 2 4 6 7 9 1113 1517
24 3802 3820 3838 3856 3874 3892 3909 3927 3945 3962 2 4 5 7 9 1112 141t!
25 3979 3997 4014 4031 4048 4065 4082 4099 4116 4133 2 3 5 7 910 1214 18
26 4150 4166 4183 4200 4216 4232 4249 4265 4281 4298 2 3 5 7 810 1113 15
27 4314 4330 4346 4362 4378 4393 4409 4425 4440 4456 2 3 5 6 8 9 1113 14
28 4472 4487 4502 4518 4533 4548 4564 4579 4594 4609 2 3 5 6 8 9 1112 14
29 4624 4639 4654 4669 4683 4698 4713 4728 4742 4757 1 3 4 6 7 9 1012 13
80 4771 4786 4800 4814 4829 4843 4857 4871 4886 4900 1 3 4 6 7 910 1113
81 4914 4928 4942 4955 4969 4983 4997 5011 5024 5038 1 3 46 7 810 1112
82 5051 5065 5079 5092 5105 5119 5132 5145 5159 5172 1 3 .45 7 8 9 1112
83 5185 5198 5211 5224 5237 5250 5263 5276 5289 5302 1 3 45 6 8 9 1012
84 5315 5328 5340 5353 5366 5378 5391 5403 5416 5428 1 3 45 6 8 9 1011
35 5441 5453 5465 5478 5490 5502 5514 5527 5539 5551 1 2 4 5 6 7 9 1011
36 5563 5575 5587 5599 5611 5623 5635 5647 5658 5670 1 2 4 5 6 7 8 1011
87 5682 5694 5705 5717 5729 5740 5752 5763 5775 5786 1 2 3 5 6 7 8 910
88 5798 5809 5821 5832 5843 5855 5866 5877 5888 5899 1 2 3 5 6 7 8 910
39 5911 5922 5933 5944 5955 5966 5977 5988 5999 6010 1 2 3 4 5 7 8 910
40 6021 6031 6042 6053 6064 6075 6085 6096 6107 6117 1 2 3 4 5 6 8 910
41 6128 6138 6149 6160 6170 6180 6191 6201 6212 6222 1 2 3 4 5 6 7 8 9
42 6232 6243 6253 6263 6274 6284 6294 6304 6314 6325 1 2 3 4 5 6 7 8 9
43 6335 6345 6355 6365 6375 6385 6395 6405 6415 6425 1 2 3 4 5 6 7 8 9
44 6435 6444 6454 6464 64_74 6484 6493 6503 6513 6522 1 2 3 4 5 6 7 8 9
45
46
6532 6542 6551 656i 6571 6580 6590 6599 6609
6628 6637 6646 6656 6665 6675 6684 6693 6702 ~m 1
1
2
2
3 4
3 4
5
5
6 7 8 9
6 7 7 8
47 6721 6730 6739 6749 6758 6767 6776 6785 6794 6803 1 2 3 4 5 5 6 7 8
48 6812 6821 6830 6839 6848 6857 6866 6875 6884 6893 1 2 3 4 4 .5 6 7 8
49 6902 6911 6920 6928 6937 6946 6955 6964 6972 6981 1 2 3 4 4 5 6 7 8
50 6990 6998 7007 7016 7024 7033 7042 7050 7059 7067 1 2 3 3 4 Ii 6 7 8
51 70711 7084 7093 7101 7110 7118 7126 7135 7143 7152 1 2 3 3 4 5 6 7 8
52 7160 7168 7177 7185 71937202 7210 7218 7226 7235 1 2 2 3 4 5 6 7 7
53 7243 7251 7259 7267 72757284 7292 7300 7308 731611 2 2 3 4 /; 6 6 7
54 7324 7332 7340 7348 73567364 7372 7380 7388 7396 1 2 2 3 4 Jj 6 6 7
* See page 13 for example. illustrating the us","of logarithmic table. in calculations.
454 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
'LOGARITHMS OF NUMBERS.-(Continued)
Proportional parts
Natural 0 i 2 3 4 5 6 7 8 9
numbers
11213141516171810
55 7404 7412 7419 7427 7435 7443 7451 7459 7466 7474 1 2 2 3 4 5 5 6 7
56 7482 7490 7497 7505 7513 7520 7528 7536 7543 7551 1 2 2 3 4 5 5 6 7
57 7559 7566 7574 7582 7589 7597 7604 7612 7619 7627 1 2 2 3 4 5 5 6 7
68 7634 7642 7649 7657 7664 7672 7679 7686 7694 7701 1 1 2 3 4 4 5 6 7
59 7709 7716 7723 77a1 7738 7745 7752 7760 7767 7774 1 1 2 3 4 4 5 6 7
60 7782 7789 7796 7803 7810 7818 7825 7832 7839 7846 1 1 2 3 4 4 5 6 6
61 7853 7860 7868 7875 7882 7889 7896 7903 7910 791~ 1 1 2 3 4 4 5 6 6
62 7924 7931 7938 7945 7952 7959 7966 7973 7980 798 1 1 2 3 3 4 5 6 6
63 7993 8000 8007 8014 8021 8028 8035 8041 8048 8055 1 1 2 3 3 4 5 5 6
64 8062 8069 8075 8082 8089 8096 8102 8109 8116 8122 1 1 2 3 3 4 5 5 6
65 8129 8136 8142 8149 8156 8162 8169 8176 8182 8189 1 1 2 3 3 4 5 5 6
66 8195 8202 8209 8215 8222 8228 8235 8241 8248 8254 1 1 2 3 3 4 5 5 6
67 8261 8267 8274 8280 8287 8293 8299 8306 8312 8319 1 1 2 3 3 4 5 5 6
68 8325 8331 8338 8344 8351 8357 8363 8370 8376 8382 1 1 2 3 3 4 4 6 6
69 8388 8395 8401 8407 8414 8420 8426 8432 8439 8445 1 1 2 2 3 4 4 5 6
70 8451 8457 8463 8470 8476 8482 8488 8494 8500 8506 1 1 2 2 3 4 4 5 6
71 8513 8519 8525 8531 8537 8543 8549 8555 8561 2 2 4
8573 8579 8585 8591 8597 8603 8609 8615 8621 ~m
1 1 3 4 5 /)
72 1 1 2 2 3 4 4 5 I)
73 8633 8639 8645 8651 8657 8663 8669 8675 8681 8686 1 1 2 2 3 4 4 I) I)
74 8692 8698 8704 8710 8716 8722 8727 8733 8739 8745 1 1 2 2 3 4 4 5 II
75 8751 8756 8762 8768 8774 8779 8785 8791 8797 8802 1 1 2 2 3 3 4 5 IS
76 8808 8814 8820 8825 8831 8837 8842 8848 8854 8859 1 1 2 2 3 3 4 5 5
77 8865 8871 8876 8882 8887 8893 8899 8904 8910 8915 1 1 2 2 3 3 4 4 5
78 8921 8927 8932 8938 8943 8949 8954 8960 8965 8971 1 1 2 2 3 3 4 4 .5
79 8976 8982 8987 8993 8998 9004 900~ 9015 9020 9026 ,1 1 2 2 3 3 4 4 5
80 9031 9036 9042 9047 9053 9058 9063 9069 9074 9079 1 1 212 3 3 4 4 5
81 9085 9090 9096 9101 9106 9112 9117 9122 9128 9133 1 1 2 2 3 3 4 4 5
82 9138 9143 9149 9154 9159 9165 9170 9175 9180 9186 1 1 2 2 3 3 4 4 .5
83 9191 9196 9201 9206 9212 9217 9222 9227 9232 9238 1 1 2 2 3 3 4 4 5
84 9243 9248 9253 9258 9263 9269 9274 92('9 9284 9289 1 1 2 2 3 3 4 4 5
85 9~4 9299 9304 9309 9315 9320 9325 9330 9335 9340 1 1 2 2 3 3 ·4 4 IS
86 9345 9350 9355 9360 9365 9370 9375 9380 9385 9390 1 1 2 2 3 3 4 4 /)
87 9395 9400 9405 9410 9415 9420 9425 9430 9435 9440 0 1 1 2 2 3 3 4 4
88 9445 9450 9455 9460 9465 9469 9474 9479 9484 9489 0 1 1 2 2 3 3 4 4
89 9494 9499 9504 9509 91?13 9518 9523 9528 9533 9538 0 1 1 2 2 3 3 4 4.
90 9542 9547 95112 9557 9562 9566 9571 9576 9581 9586 0 1 1 2 2 3 3 4 4.
91 9590 9595 9600 9605 9609 9614 9619 9624 9628 9633 0 1 1 2 2 3 3 4 4.
92. 9638 9643 9647 9652 9657 9661 9666 9671 9675 9680 0 1 1 2 2 3 3 4 4
93 9685 9689 9694 9699 9703 9708 9713 9717 9722 9727 0 1 1 2 2 3 3 4 4.
94 9731 9736 9741 9745 97!i0 9754 9759 9763 9768 97;,?3 0 1 1 2 2 3 3 4 4.
95 0777 9782 9786 9791 9795 9800 9805 9809 9814 9818 0 1 1 2 2 3 3 4 4.
96 9823 9827 9832 9836 9841 9845 981)0 9854 9859 9863 0 1 1 2 2 3 3 4 4
97 9868 9872 9877 9881 9886 9890 9894 9899 9903 9908 0 1 1 2.2 3 3 4 4.
98 9912 9917 9921 9926 9930 9934 9939 9943 9948 9952 0 1 1 2 2 3 3 4 4
99 99b6 9961 9965 9969 9974 9978 9983 9987 9991 9996 0 1 1 2 2 3 3 3 4.
APPENDIX 455
ANTlLOGAlUTHMS
,Proportional pa.rts
Logarithms 0 1 2 3 4 5 6 7 8 9
1\2\3\415\6\7181~
.00 1000 1002 1005 1007 1009 1012 1014 1016 1019 1021 a a 1 1 1 1 2 2 2
.01 1023 1026 1028 1030 1033 1035 1038 1040 1042 1045 0 0 1 1 1 1 2 2 2
.02 1047 1050 1052 1054 1057 1059 1062 1064 1067 1069 0 0 1 1 1 1 2 2 2
.03 1072 1074 1076 1079 1081 1084 1086 1089 1091 1094 0 0 1 1 1 1 2 2 2
.04 1096 1099 1102 1104 1107 1109 1112 1114 1117 1119 0 1 1 1 1 2 2 2 2
.05 1122 1125 1127 1130 1132 1135 1138 1140 1143 1146 0 1 1 1 1 2 2 2 2
.06 1148 1151 1153 1156 1159 1161 1164 1167 1169 1172 0 1 1 1 1 2 2 2 2
.07 1175 1178 1180 1183 1186 1189 1191 1194 1197 1199 0 1 1 1 1 2 2 2 2
.08 1202 1205 1208 1211 1213 1216 1219 1222 1225 1227 0 1 1 1 1 2 2 2 3
.09 1230 1233 1236 1239 1242 1245 124'1 1250 1253 1256 0 1 1 1 1 2 2 2 a
.10 1259 1262 1265 1268 1271 1274 1276 1279 1282 1285 0 1 1 1 1 2 2 2 3
.11 1288 1291 1294 1297 1300 1303 1306 1309 1312 1315 0 1 1 1 2 2 2 2 3
.12 1318 1321 1324 1327 1330 1334 1337 1340 1343 1346 0 1 1 1 2 2 2 2 3
.13 1349 1352 1355 1358 1361 1365 1368 1371 1374 1377 0 1 1 1 2 2 2 3 3
.14 1380 1384 1387 1390 1393 1396 ~400 1403 1406 1409 0 1 1 1 2 2 2 3 3
.15 1413 1416 1419 1422 1426 1429 1432 1435 1439 1442 0 1 1 1 2 2 2 3 3
.16 1445 1449 1452 1455 1459 1462 1466 1469 1472 1476 0 1 1 1 2 2 2 3 3
.17 1479 1483 1486 1489 1493 1496 1500 1503 1507 1510 0 1 1 1 2 2 :I 3 3
.18 1514 1517 1521 1524 152~ 1531 1535 1538 1542 1545 0 1 1 1 2 2 2 3 a
.19 1549 1552 1556 1560 156 1567 1570 1574 1578 1581 0 1 1 1 2 2 3 3 3
.20 1585 1589 1592 1596 1600 1603 1607 1611 1614 1618 0 1 1 1 2 2 3 3 3
.21 1622 1626 1629 1633 1637 1641 1644 1648 1652 1656 0 1 1 2 2 2 3 3 3
.22 1660 1663 1667 1671 1675 1679 1683 1687 1690 1694 0 1 1 2 2 2 3 3 3
.23 1698 1702 1706 1710 1714 1718 1722 1726 1730 1734 0 1 1 2 :I 2 3 3 4,
.24 1738 1742 1746 1750 1754 1758 1762 1766 1770 1774 0 1 1 2 2 2 3 3 4,
.25 1778 1782 1786 1791 1795 1799 1803 1807 1811 1816 0 1 1 2 2 2 3 8 4
.26 1820 1824 1828 1832 1837 1841 1845 1849 1854 1858 0 1 1 2 2 3 3 3 4
.27 1862 1866 1871 1875 1879 1884 1888 1892 1897 1901 0 1 1 2 2 3 3 3 4
.28 1905 1910 1914 1919 1923 1928 1932 1936 1941 1945 0 1 1 2 2 3 3 4 4
.29 1950 1954 1959 1963 1968 1972 1977 1982 1986 1991 0 1 1 2 2 3 3 4 ,4
.30 1995 2000 2004 2009 2014 2018 2023 2028 2032 2037 0 1 1 2 2 3 3 4 4
.31 2042 2046 2051 2056 2061 2065 2070 2075 2080 2084 0 1 1 2 2 3 3 4 4,
.32 2089 2094 2099 2104 2109 2113 2118 2123 2128 2133 0 1 1 2 2 3 3 4 4
.33 2138 2143 2148 2153 2158 2163 2168 2173 2178 2183 0 1 1 2 2 3 3 4 4
.34 2188 2193 2198 2203 2208 2213 2218 2223 2228 2234 1 1 2 2 3 3 4 4 Ii
,
.35 2239 2244 2249 2254 2259 2265 2270 2275 2280 2286 1 1 2 2 3 3 4 4 Ii
.36 2291 2296 2301 2307 2312 2317 2323 2328 2333 :1339 1 1 2 2 3 3 4 4 5
.37 2344 2350 2355 2360 2366 2371 2377 2382 2388 2393 1 1 2 2 3 3 4 4 Ii
.3S 2399 2404 2410 2415 2421 2427 2432 2438 2443 2449 1 1 2 2 3 3 4 4 Ii
.39 2455 2460 2466 2472 2477 2483 2489 2495 2500 2506 1 1 2 2 3 3 4 5 5
"
.40 2512 2518 2523 2529 2535 2541 2547 2553 2559 2564 1 1 2 2 3 4 4 5 II
.41 2570 2576 2582 2588 2594 2600 2606 2612 2618 2624 1 1 2 2 3 4 4 5 8
.42 2630 2636 2642 2649 2655 2661 2667 2673 2679 2685 1 1 2 2 3 4 4 IS 6
.43 2692 2698 2704 2710 2716 2723 2729 2735 2742 2748 1 1 2 3 3 4 4 5 6
.44 2754 2761 2767 2773 2780 2786 2798 2799 2805 2812 1 1 2 3 3 4 4 II 6
.45 2818 2825 2831 2838 2844 2851 2858 2864 2871 2877 1 1 2 3 3 4 5 IS 6
.46 2884 2891 2897 2904 2911 291.7 2924 2981 2938 2944 1 1 2 3 3 4 5 5 6
.47 2951 2958 2965 2972 2979 2985 2992 2999 3006 3013 1 1 2 3 3 4 5 5 6
.48 3020 3027 3034 3041 3048 3055 3062 3069 3076 3083 1 1 2 3 4 4 5 6 6
.49 3090 3097 3105 3112 3119 3126 3138 3141 3148 3155 1 1 2 3 4 4 5 6 6
456 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
ANTILOGARITHMs.-(Cantinued)
Proportional parts
Logarithms 0 1 2 3 4 "5 6 7' 8 9
11213141516171819
.50 3162 3170 3177 3184 3192 3199 3206 3214 3221 3228 1 1 2 3 4 4 5 6 7
.51 3236 3243 3251 3258 3266 3273 3281 3289 3296 3304 1 2 2 3 4 5 5 6 7
.52 3311 3319 3327 3334 3342 3350 3357 3365 3378 3381 1 2 2 3 4 5 5 6 7
.53 3388 3396 3404 3412 3420 3428 3436 3443 3451 3459 1 2 2 3 4 5 6 6 7
.54 3467 3475 3483 3491 3499 3508 3516 3524 3532 3540 1 2 2 3 4 5 6 6 7
.55 3548 3556 3565 3573 3581 3589 3597 3606 3614 3622 1 2 2 3 4 5 6 7 7
.56 3631 3639 3648 3656 3664 3673 3681 3690 3698 3707 1 2 3 3 4 5 6 7 8
.57 3715 3724 3733 3741 3750 3758 3767 3776 3784 3793 1 2 3 3 4 5 6 7 8
.58 3802 3811 3819 3828 3837 3846 3855 3864 3873 3882 1 2 3 4 4 5 6 7 8
.59 3890 3899 3908 3917 3926 3936 3945 3954 3963 3972 1 2 3 4 5 5 6 7 8
.60 3981 3990 3999 4009 4018 4027 4036 4046 4055 4064 1 2 3 4 5 6 6 7 8
.61 4074 4083 4093 4102 4111 4121 4130 4140 4150 4159 1 2 3 4 5 6 7 8 9
.62 4169 4178 4188 4198 4207 4217 4227 4236 4246 4256 1 2 3 4 5 6 7 8 I)
.63 4266 4276 4285 4295 4305 4315 4325 4335 4345 4355 1 2 3 4 5 6 7 8 9
.64 4365 4375 4385 4395 4406 4416 4426 4436 4446 4457 1 2 3 4 5 6 7 8 9
.65 4467 4477 4487 4498 4508 4519 4529 4539 4550 4560 1 2 3 4 5 6 7 8 9
.66 4571 4581 4592 4603 4613 4624 4634 4645 4656 4667 1 2 3 4 5 6 7 910
.67 4677 4688 4699 4710 4721 4732 4742 4753 4764 4775 1 2 3 4 5 7 8 910
.68 4786 4797 4808 4819 4831 4842 4853 4864 4875 488 1 2 3 4 6 7 8 910
.69 4898 4909 4920 4932 4943 495/? 4966 4977 4989 5000 1 2 3 5 6 7 8 910
.70 5012 5023 5035 5047 5058 5070 5082 5093 5105 5117 1 2 4 5 6 7 8 9 11
.11 5129 5140 5152 5164 5176 5188 5200 5212 5224 5236 1 2 4 5 6 7 810 11
.72 5248 5260 5272 5284 5297 5309 5321 5333 5346 5358 1 2 4 5 6 7 910 11
5370 5383 5395 5408 5420 5433 5445 5458 5470 5483 4 5 6 8 910 11
5495 5508 5521 5534 5546 5559 5572 5585 5598 5610 ~ ~ 4 5 6 8
.73
.74 910 12
.75 5623 5636 5649 5662 5675 5689 5702 5715 5728 5741 1 3 4 5 7 8 9101 2
.76 5154 5768 5781 5794 5808 5821 5834 5848 5861 5875 1 3 4 5 7 8 9 1112
.77
.78
5888 5902 5916 5929 5943 5957 5970 5984 5998 6012
6026 6039 6053 6067 6081 6095 6109 6124 6138 6152
1
1
3
3 ! Ig
7 810 1112
7 810 1113
.79 6166 6180 6194 6209 6223 6237 6252 6266 6281 6295 1 3 4 6 7 910 1113
.80 6310 6324 6"389 6353 6368 6383 6397 6412 6427 6442 1 3 4 6 7 910 1218
6457 6471 6486 6501 6516 6531 6546 6561 6577 6592 2 3 5 8 911 1214
5 ~ 8 9 11121 4
.81
.82 6607 6622 6637 6653 6668 6683 6699 6714 6730 6745 2 3
.83 6761 6776 6792 6808 6823 6839 6855 6871 6887 6902 2 3 5 6 8 9 111314
.84 6918 6934 6950 6966 6982 6998 7015 7031 7p47 7063 2 3 5 6 810 11131 5
.85 7079 7096 7112 7129 7145 7161 7178 7194 7211 7228 2 3 5 7 810 12131 5
.86 7244 7261 7278 7295 7311 7328 7345 7362 7379 7396 2 3 5 7 810 1213 15
.87 7413 7430 7447 7464 7482 7499 7516 7534 7551 70682 3 5 7 910 1214 16
.88 7586 7603 7621 7638 7656 7674 7691 7709 7727 7745 2 4 5 7 911 1214 16
.89 7762 7780 7798 7816 7834 7852 7870 7889 7907 7925 2 4 5 7 911 13 14 16
.90 7943 7962 7980 7998 8017 8035 8054 8072 8091 8110 2 4 6 7 911 13 15 17
.91 8128 8147 8166 8185 8204 8222 8241 8260 8279 8299 2 4 6 8 911 13 15 17
.92 8318 8337 8356 8375 8395 8414 8433 8453 8472 8492 2 4 6 8 10 12 14 15 17
.93 8511 8531 8551 8570 8590 8610 8630 8650 8670 8690 2 4 6 810 12 14 16 18
.94 8710 8730 8750 8770 8790 8810 8831 8851 8872 8892 2 4 6 8 10 12 14 16 18
.95 8913 8933 8954 8974 8995 9016 9036 9057 9078 9099 2 4 6 810 12 15 1719
.96 9120 9141 9162 9183 9204 9226 9247 9268 9290 9311 2 4 6 811 13 15 1719
.97 9333 9354 9376 9397 9419 9441 9~62 9484 9506 9528 2 4 7 911 13 15 1720
.98 9550 9572 9594 9616 9638 9661 9683 9705 9727 9750 2 4 7 911 13 16 1820
.99 9772 9795 9817 9840 9863 9886 9908 9931 9954 9977 2 5 7 911 14 16 18 2()
INDEX
A ~ldehyde content, assay of volatile
oils for, 372
Abbe refractometer, 242 Alkalimetry, 86
diagram of, 243 direct titration methods, 86
illustration of, 242 table of official substances as-
temperature control for, 244 sayed by, 91
Absolute viscosity, 257 residual titration methods, 90
Absorption pipette, 191 table of substances assayed by,
Acacia, moisture content, deter- 103
mination of, 331 Alkaloidal assaying, 386
Accuracy and honesty, 3 by aliquot-part method, 403
Acetylization flask, 368 decanting the aliquot portion,
Acetylsalicylic acid tablets, assay of, 396
111 determination of the alkaloidal
Acid number, 245 content, 401
Acid value, 345 extraction of the drug, 395
definition of, 345 shaking out with acid, 398
determination of, 347 with immiscible solvent, 399
table of official substances with table of official substances as-
limits, 348 sayed by, 411
Acid-base equilibrium, 272 emulsification in, 389
Acidimetry, 105 general procedures, 394
and alkalimetry, 65 type methods, 403
direct titration methods, 105 principles applied in, 386
table of substances assayed by, sources of error in, 390
112 by special methods, 418
residual titration methods, 110 by total-extraction method, 411
table of substances assayed by, percolator recommended for,
114 398
Acid-insoluble ash, 323 table of official substances as-
Acidity index, 345 sayed by, 416
Alkaloidal salts, assay of, 431
Adsorbents in alkaloidal assays, 402
table of those official salts assayed
Alcohol, determination of, 214
for content of alkaloid, 436
Alcoholic potassium hydroxide, 365 Alkaloidal test solutions, 393
Alcohol-soluble extractive, 339 Alkaloidal titrations, choice of indi-
table of official substances with cators for, 392
limits of, 340 Alkaloids, gravimetric determina-
Alcohols, assay of volatile oils for, tion of, 403
368 volumetric determination of, 407
457
458 QUANTITATIVE PHARMACEUTICAL CHEMISTRY
L N
ViSCOSimeter, 258 X
ViSCOSity, definition of, 256 Xylene moisture method, 331
determination of, 259
units of, 257 z
Volatile ether-soluble extractive, 337 Zinc oxide, assay of, 92