PHAN111LEC_WEEK 8 Preparation and Standardization of 0.
1 N Silver
Precipitimetry/Argentometry/Saturation
Method
• Árgentum = silver
• Determination of Halide-ions: bromide,
chloride, mercury, fluoride, iodide → when
combined with silver, mercury or lead,
produces precipitate
• Sample is titrated with a standard solution of
a precipitating agent in the presence of a
suitable indicator
Principles
1) Solubility Product Principle
• Solubility Product Constant (Ksp) –
equilibrium constant of at solid
dissolving at a solution; represents
the level of solubility; the more
soluble, the higher the Ksp
If Ionic product exceeds the Ksp, precipitation
occurs; if Ksp is less than Ksp, no precipitation
Ex.
𝑁𝑎𝐶𝑙 + 𝐴𝑔𝑁𝑂3 → 𝐴𝑔𝐶𝑙 ↓ + 𝑁𝑎𝑁𝑂3
Analytes
2) Those which form a very slightly soluble
substance (precipitate) with the compound
in the standard solution
• NaCl
• 𝐾𝐶𝑙3
• Thiamine HCl
• Mustine Chloride – nitrogen mustard
solution for anti-cancer therapeutics
• Carbromal – hypnotic sedative; in
combination with phenobarbital
Standard Solutions
3) Substances:
• 𝐴𝑔𝑁𝑂3
• 𝑁𝐻4 𝑆𝐶𝑁
• 𝐾𝑆𝐶𝑁
Preparation and Standardization of 0.1 N Silver
Nitrate
4) Standard Solution – Silver Nitrate Sol.
5) Primary Standard: Analytical Grade Sodium
Chloride
Ammonium Thiocynate
6) Standard Solution – Ammonium Thiocyanate
7) Secondary Standard – 0.1 N Silver Nitrate
ENDPOINT DETERMINATION
1. Cessation of precipitation or appearance of
turbidity
2. Instrumental Methods
a. When precipitate is being weighed, it
becomes gravimetric method of
analysis
b. Potentiometric Titration – use of
electrodes (through potentiometer)
to measure the potentials of the
solution during the titration process;
good for colored substances but a
slow, sensitive process for the
reading to stabilize
3. Use of internal indicators
a. Colored Ion/Volhard’s Method by
Jacob Volhard
i. For chloride determination
ii. Ferric Alum or Ammonium
Iron (III) Sulfate (FAS) or
𝐹𝑒𝑁𝐻4 (𝑆𝑂4 )2 is used using
Ammonium Thiocyanate VS
or 𝑁𝐻4 𝑆𝐶𝑁 as 2nd VS to
produce Ferric Thiocyanate
which is responsible for the
reddish-brown color
endpoint
iii. Residual Titration
iv. Nitric Acid is used to prevent
precipitation of silver as
carbonate or phosphate,
prevent hydrolysis of ferric
alum to form ferric oxide
v. Acidic medium & NH4SCN
inc. solubility which leads to
titration reading errors;
solutions include:
1. Nitrobenzene is used
to form a film for AgCl
to prevent reaction
with NH4SCN
2. Filtration of the
precipitate
Ex.
𝑁𝑎𝐶𝑙 + 𝐴𝑔𝑁𝑂3 → 𝐴𝑔𝐶𝑙 ↓ + 𝑁𝑎𝑁𝑂3
𝐴𝑔𝑁𝑂3 𝑒𝑥𝑐𝑒𝑠𝑠 + 𝑁𝐻4 𝑆𝐶𝑁 → 𝐴𝑔𝑆𝐶𝑁 + 𝑁𝐻4 𝑁𝑂3
 𝐹𝑒𝑁𝐻4 (𝑆𝑂4 )2 + 3𝑁𝐻4 𝑆𝐶𝑁 or
→ 𝑭𝒆(𝑺𝑪𝑵)𝟑 + 2(𝑁𝐻4 )2 𝑆𝑂4 2𝐶𝑁 − + 𝐴𝑔 → 𝐴𝑔(𝐶𝑁)2 ↓

b. Colored Secondary iii. Denige’s Method

Precipitate/Mohr’s Method by
Friedrich Mohr
i. Direct Method
ii. Potassium Chromate or
𝐾2 𝐶𝑟𝑂 is used; yellowish,
crystalline organic compound
that yields toxic fumes when
heating, strong oxidation
agent used in textile dying
iii. Endpoint is a reddish
secondary precipitate
iv. Used to measure fluoride
ions
v. Neutral medium should be
used; if alkaline, it produces
NaOH, if acidic, CrO will
become a dichromate
Ex.
1. For iodide ions
e. Gay Lussac’s Method
i. no indicator
ii. based on flocculation
(amalgamation/clumping)
iii. not reliable
Calculations
8) Gram equivalent weight is obtained by
dividing the molecular weight by the total
valence of the precipitating or precipitated
ion
𝑀𝑊
𝑔. 𝑒𝑞. =
𝑓
9) Precipitation methods can be divided into
direct and residual methods
For Direct:

𝑁𝑎𝐶𝑙 + 𝐴𝑔𝑁𝑂3 → 𝐴𝑔𝐶𝑙 ↓ + 𝑁𝑎𝑁𝑂3 (𝑚𝐿) (𝑁) (𝑚𝐸𝑞)

𝐴𝑔𝑁𝑂3 + 𝐾2 𝐶𝑟𝑂 → 𝑨𝒈𝑪𝒓𝑶 ↓ + 𝐾𝑁𝑂3 %= 𝑥 100
𝑤𝑡

c. Colored Adsorption Product/Fajan’s For Residual:

Method by Kazimiers Fajan
i. Dicholorofluorescein is used
that adheres to the surface of
AgCl to make it negatively
charged
ii. From greenish yellow
fluorescence to the endpoint
of reddish-pink color
iii. Excess titration
iv. Fluorescein TS is a weak acid,
which means that pH of soln.
should be slightly alkaline to
keep the indicator in an anion
state
Ex.
𝑁𝑎𝐶𝑙 + 𝐴𝑔𝑁𝑂3 → 𝐴𝑔𝐶𝑙 ↓ + 𝑁𝑎𝑁𝑂3
𝐴𝑔𝐶𝑙− + 𝐴𝑔𝑁𝑂3 𝑒𝑥𝑐𝑒𝑠𝑠 → 𝑨𝒈𝑭 𝑐𝑜𝑚𝑝𝑜𝑢𝑛𝑑
UNOFFICIAL USP METHODS
d. Turbidity/Liebig’s Method
i. For assay of cyanide
ii. Permanent cloudy/murky
solution
Ex.
𝐾𝐶𝑁 + 𝐴𝑔𝑁𝑂3 → 𝐾𝐴𝑔(𝐶𝑁)2 ↓ + 𝐾𝑁𝑂3
[(𝑁1 𝑉1 ) − (𝑁2 𝑉2 )] (𝑚𝐸𝑞)
%= 𝑥 100
𝑤𝑡
Practice
1. A sample of ammonium bromide weighing
0.4128 g was dissolved in water, acidifed
with HNO3 and 50 mL of 0.1 N AgNO3
solution added. The excess of the latter
required 16.5 mL of 0.05015 N NH4SCN
solution for titration. What is the percentage
purity of NH4Br in the sample?
𝑁𝐻4 𝐵𝑟 = 14 (1) + 1 (4) + 80 (1)
= 98 / 1(1000)
= 0.098 𝑔/𝑚𝐸𝑞
[(𝑁1 𝑉1 ) − (𝑁2 𝑉2 )] (𝑚𝐸𝑞)
%= 𝑥 100
𝑤𝑡
%
[(0.1 𝑁 𝑥 50 𝑚𝐿) − (0.05015 𝑁 𝑥 16.5 𝑚𝐿)] (0.098 𝑔/𝑚𝐸𝑞)
=
0.4128 𝑔
𝑥 100
% = 𝟗𝟗. 𝟎𝟔 % 𝒐𝒇 𝑵𝑯𝟒𝑩𝒓
2. What volume of 0.05015 N thiocyanate
solution would be required to titrate the
excess from 50 mL of 0.1 N AgNO3 that was
 added to a solution of 0.2215 g of NH4Cl
which is 99.5% pure? [(𝑁1 𝑉1 ) − (𝑁2 𝑉2 )] (𝑚𝐸𝑞)
%𝑁𝑎𝐶𝑙 = 𝑥 100
𝑤𝑡
𝑁𝐻4 𝐶𝑙 = 14 (1) + 1 (4) + 35(1) %𝑁𝑎𝐶𝑙 =
[(25 mL x 0.1 N ) − (12 mL x 0.09524 N )] (0.058 𝑔/𝑚𝐸𝑞)
𝑥 100
0.1423 𝑔
= 53 / 1(1000)
%𝑁𝑎𝐶𝑙 = 𝟒𝟓. 𝟕𝟖% 𝒐𝒇 𝑵𝒂𝑪𝒍
= 0.053 𝑔/𝑚𝐸𝑞

[(𝑁1 𝑉1 ) − (𝑁2 𝑉2 )] (𝑚𝐸𝑞)

[(𝑁1 𝑉1 ) − (𝑁2 𝑉2 )] (𝑚𝐸𝑞) %𝑁𝑎𝐵𝑟 = 𝑥 100
%= 𝑥 100 𝑤𝑡
𝑤𝑡 [(25 mL x 0.1 N ) − (12 mL x 0.09524 N )] (0.103 𝑔/𝑚𝐸𝑞)
%𝑁𝑎𝐵𝑟 = 𝑥 100
% [(𝑁1 𝑉1 ) − (𝑁2 𝑉2 )] (𝑚𝐸𝑞) 0.1423 𝑔
= %𝑁𝑎𝐵𝑟 = 𝟗𝟖. 𝟐𝟑% 𝒐𝒇 𝑵𝒂𝑩𝒓
100 𝑤𝑡
% (𝑤𝑡) = [(𝑁1 𝑉1 ) − (𝑁2 𝑉2 )] (𝑚𝐸𝑞)
% (𝑤𝑡) [(𝑁1 𝑉1 ) − (𝑁2 𝑉2 )] (𝑚𝐸𝑞) 4. A 0.2182 g sample of NaCl was assayed by
=
𝑚𝐸𝑞 𝑚𝐸𝑞 the Volhard method using 50.00 mL of
% (𝑤𝑡) 0.0985 N silver nitrate and 11.75 mL of
= (𝑁1 𝑉1 ) − (𝑁2 𝑉2 ) 0.1240N ammonium thiocyanate Calculate
𝑚𝐸𝑞
1 % (𝑤𝑡) 1 the percent NaCl in the sample.
[(𝑁2 𝑉2 )] = [ − (𝑁1 𝑉1 ) +]
𝑁2 𝑚𝐸𝑞 𝑁2
𝑁𝑎𝐶𝑙 = 23 (1) + 35 (1)
% (𝑤𝑡) (𝑁1 𝑉1 )
𝑉2 = − = 58/1(1000)
𝑚𝐸𝑞 𝑥 𝑁2 𝑁2 = 0.058 𝑔/𝑚𝐸𝑞
0.995 (0.2215 g) (0.1 N x 50 mL ) [(𝑁1 𝑉1 ) − (𝑁2 𝑉2 )] (𝑚𝐸𝑞)
𝑉2 = − %𝑁𝑎𝐶𝑙 = 𝑥 100
0.053 𝑔 𝑥 0.05015 N 0.05015 N 𝑤𝑡
𝑉2 = 𝟏𝟔. 𝟕𝟖 𝒎𝑳 𝒐𝒇𝟎. 𝟎𝟓𝟎𝟏𝟓 𝐍 𝐭𝐡𝐢𝐨𝐜𝐲𝐚𝐧𝐚𝐭𝐞 𝐬𝐨𝐥𝐮𝐭𝐢𝐨𝐧 %𝑁𝑎𝐶𝑙 =
[(0.0985 N 𝑥 50.00 mL) − (0.1240N x 11.75 mL)] (0.058 𝑔/𝑚𝐸𝑞)
𝑥 100
0.2182 g

3. A mixture consisting of pure NaCl and pure %𝑁𝑎𝐵𝑟 = 𝟗𝟐. 𝟏𝟖% 𝒐𝒇 𝑵𝒂𝑪𝒍
NaBr weighs 0.2845 g. It was dissolved in 20
mL of purified water in a 100 mL volumetric
flask, 50 mL of 0.1 N AgNO3 and 3 mL of
HNO3 added diluted with purified water to
the mark, stoppered and shaken thoroughly
until the mixture was uniform. This was
filtered and the first 20 mL of the filtrate
was discarded. The next 50 mL of the filtrate
was treated with 2 mL of ferric alum
indicator solution and titrated with 0.09524
N ammonium solution requiring 12 mL of
the latter to reach the endpoint. What is the
percentage of NaBr and NaCl in the sample?

0.2845 𝑔
𝑥 50 𝑚𝐿 = 0.1423 𝑔 𝑜𝑓 𝑁𝑎𝐶𝑙 𝑎𝑛𝑑 𝑁𝑎𝐵𝑟
100 𝑚𝐿
50 𝑚𝐿
𝑥 50 𝑚𝐿 = 25 𝑚𝐿 𝑜𝑓 𝐴𝑔𝑁𝑂3
100 𝑚𝐿

𝑁𝑎𝐶𝑙 = 23 (1) + 35 (1)

= 58/1(1000)
= 0.058 𝑔/𝑚𝐸𝑞

𝑁𝑎𝐵𝑟 = 23 (1) + 80 (1)

= 103/1(1000)
= 0.103 𝑔/𝑚𝐸𝑞
 PHAN111LEC_WEEK 9
COMPLEXOMETRY/COMPLEXIMETRY
1. Analysis of metals
2. Determine hardness of water due to calcium
and magnesium salts, calcium compounds,
and their preparations, and determination of
deficiencies in the body’s minerals
Hardness in water is due to the presence of Ca and
Mg salts; soaps cannot foam; can clog pores and
cause itching and flaking; can cause kidney stones
Temporary Hardness is caused by bicarbonates and
can be destroyed by boiling
Permanent Hardness is caused by sulfates and
chlorides of Ca and Mg and cannot be affected by
boiling
Total Hardness – represented by combined
temporary and permanent hardness and can be
determined by titration with EDTA
• Recommended conc. for drinking water
o 40-80 ppm Ca content
o 20-30 ppm Mg content
o Total hardness of both must be 2-4
moles/L
Conc. as CaCO3 Indication
0-60 mg/L Soft water
60-120 mg/L Moderately hard water
120-180 mg/L Hard water
>180 mg/L Very hard water
3. Formation of a complex substance
4. EDTA (Ethylenediaminetetraacetic acid)
reaction with metal ions to form a water-
soluble stable complex or a chelate
compound
o Standardized with CACO3
o Indicators used: Hydroxynapthol-
blue TS, Eriochrome Black TS, or
Dithiazone TS
Principle and Concepts
• When a metal ion combines with a molecule
which donate electrons (reducing agents) =
complex
• When a metal ion combines with a molecule
that contains two or more groups that
donate electrons = chelate
• Ligand – electron pair donor or a Lewis base;
HNP is used for calcium-containing compounds
Eriochrome Black TS is used for zinc-containing
compounds
has the ability to bind with the metal ion and
produce a complex
o Monodentate/Unidentate
▪ “one-toothed”; donates one
pair of electron
▪ Forms more stable complexes
than polydentates
o Polydentate/Multidentate
▪ “many toothed”; donates
more than one pair
▪ Example: EDTA which is a
hexadentate
• metal ion with chelating agents
• Chelating Agents – substance that can form
several bonds with a metal; multidentate
ligand; forms complexes that are insol. in
water, but sol. In organic solvents; used to
prevent further reaction of the metal ion
without removing it from the solution
o Examples: Dimethylglyoxime and
Salicylaldoxime
• Sequestering Agents – chelating agents that
form water-soluble complexes with metal
ions; used to remove water hardness
o Combines with calcium and
magnesium ions and other heavy
metals
Indicators
• Qualities of a good indicators are:
o Sharp color change at endpoint
o Specificity of the indicator for the
metal ion under the conditions of
the analysis
o Have a stability constant smaller
than that of the metal-EDTA
complex
o Indicator must give up the metal ion
to the titrant EDTA for complexing
o Should not compete with the EDTA
 unreactive to other chelating agents or form
a more stable complex with EDTA
Ex.
𝑀𝑛 + 𝑀𝑔𝐸𝐷𝑇𝐴 → 𝑀𝑔 + 𝑀𝑛𝐸𝐷𝑇𝐴

4. Indirect Titration – used for determination

of ions that do not react with EDTA;
protons from disodium EDTA are displaced
by heavy metal and titrated with sodium
alkali
Ex.
Assay of barbiturates using mercuric ion solution

Factors That Increases Selectivity in EDTA

• Use of masking agents and de-masking
agents
EDTA/Ethylenediaminetetraacetic Acid
o Masking - used to indicate the
• Unselective reagent because it can form
determination of a metal in the
complexes with many charged cations
presence of another metal through
• Disodium salt is preferred over the free acid adjusting the pH or with the use of
in preparing standard sol. of EDTA due to: auxiliary complexing agents such as:
o Being more water-soluble TEA, Thioglycols, Potassium cyanide,
o Non-hygroscopic ammonium fluoride, ascorbic acid,
o Very stable
tartrates, and citrates
• Chemical formula: 𝐶10 𝐻14 𝑁2 𝑁𝑎2 𝑂8 • 2𝐻2 𝑂 ▪ Masking by precipitation
• MW: 372.24 g/mEq ▪ Masking by complex
• Standardization: formation
o An accurately weighed sample of o De-masking – masked substances
calcium carbonate is diluted with 50 regains its ability to enter into a
mL of water, sufficient dilute HCl reaction
acid is added to dissolve the
carbonate and then is then diluted to
150 mL. The mixture is titrated with
EDTA. Calculate the M of the
volumetric solution.

TYPES OF COMPLEXOMETRIC TITRATIONS

1. Direct Titration – simplest and most
convenient method similar to acid-base
titrations but is a slow complex formation;
Ex.
Assay of Calcium Chloride

2. Residual Titration – standard EDTA is added

to the metal solution, excess is backtitrated
• pH control – based on differences in
with another standard solution
stability of the chelates formed between the
Ex.
metal ions and the chelating agent as
Determination of Manganese (EDTA, Zinc VS,
stability of metal complex is pH dependent;
Eriochrome Black TS)
most ligands are basic and bind to H+ ions
hence, ↓pH = less stable
3. Replacement Titration/Substitution – metal
• Use of selective metal indicator – should be
to be analyzed displaces quantitatively from
sufficiently rapid to establish end point
the complex; used for metals that are
without undue waiting
 • Classical Separation – separate ion using dissolved in 500 mL of a solvent. Another 50
precipitation, then redissolve into a solution mL portion of the water sample was treated
for determination with K2C2O4 (potassium oxalate) and the
Ex. resulting mixture consumed 10 mL of EDTA.
CaC2O4, nickel dimethylglyoximate, and CUSCN Find the hardness in ppm in terms of
Calcium Carbonate. Interpret your result.
• Solvent Extraction – separation of metal by
adding excess solution to which will be 𝐶𝐴𝐶𝑂3 = 40(1) + 12 (1) + 16 (3)
diluted in water with EDTA, and then will be = 100 𝑔/𝑚𝑜𝑙
determined
Ex. 0.2155 g
𝑥 25 𝑚𝐿 = 0.0108 𝑔 𝑜𝑓 𝐶𝐴𝐶𝑂3
Zinc can be separated from copper and lead by 500 𝑚𝐿
adding excess ammonium thiocyanate solution and
extracting the resulting zinc thiocyanate with 4- 𝑤𝑡
𝑀=
methylpentan-2-one (isobutyl methyl ketone); the 𝑀𝑊 𝑥 𝐿
0.0108 𝑔
extract is diluted with water with EDTA solution 𝑀=
and the zinc content is determined 100 𝑔/𝑚𝑜𝑙 𝑥 0.02065 𝐿
𝑀 = 0.0052 𝑀 𝑜𝑟 𝑚𝑜𝑙/𝐿 𝑜𝑓 𝐸𝐷𝑇𝐴
• Removal of Anions – anions can interfere 0.0052 𝑚𝑜𝑙 𝐸𝐷𝑇𝐴 100 𝑔 1000 𝑚𝑔
with complexometric titrations; they are 𝑚𝑔 𝑜𝑓 𝐶𝐴𝐶𝑂3 (1𝑠𝑡) = 32.50 mL 𝑥
1000 𝑚𝐿
𝑥
1 𝑚𝑜𝑙
𝑥
1𝑔
removed using ion exchange resins = 16.9 𝑚𝑔 𝑜𝑓 𝐶𝐴𝐶𝑂3 𝑖𝑛 𝑤𝑎𝑡𝑒𝑟

Ex. 1𝐿
Used in water filtration 50 𝑚𝐿 𝑥 = 0.050 𝐿
1000 𝑚𝐿

• Kinetic Masking – special case in which 16.9 𝑚𝑔

𝑝𝑝𝑚 =
metal ion does not effectively enter into 0.050 𝐿
complexation because of its kinetic inertness 𝑝𝑝𝑚 = 𝟑𝟑𝟖 𝒎𝒈/𝑳 𝒘𝒉𝒊𝒄𝒉 𝒄𝒐𝒏𝒄𝒍𝒖𝒅𝒆𝒔 𝒕𝒐 𝒂 𝒗𝒆𝒓𝒚 𝒉𝒂𝒓𝒅 𝒘𝒂𝒕𝒆𝒓
(little to no ability to react); masking
kinetically to speed the rate of reaction 0.0052 𝑚𝑜𝑙 𝐸𝐷𝑇𝐴 100 𝑔 1000 𝑚𝑔
𝑚𝑔 𝑜𝑓 𝐶𝐴𝐶𝑂3 (2𝑛𝑑) = 10 mL 𝑥 𝑥 𝑥 = 16.9 ==
1000 𝑚𝐿 1 𝑚𝑜𝑙 1𝑔
Practice = 5.2 𝑚𝑔 𝑜𝑓 𝐶𝐴𝐶𝑂3 𝑖𝑛 𝑤𝑎𝑡𝑒𝑟

1. A 50 mL water sample was determined for 5.2 𝑚𝑔

hardness in terms of CaCO3. It required 40 𝑝𝑝𝑚 =
0.050 𝐿
mL of a 0.01 M EDTA solution for titration. 𝑝𝑝𝑚
Calculate the total hardness in ppm (mg/L). = 𝟏𝟎𝟒 𝒎𝒈/𝑳 𝒘𝒉𝒊𝒄𝒉 𝒄𝒐𝒏𝒄𝒍𝒖𝒅𝒆𝒔 𝒕𝒐 𝒎𝒐𝒅𝒆𝒓𝒂𝒕𝒆𝒍𝒚 𝒉𝒂𝒓𝒅 𝒘𝒂𝒕𝒆𝒓
Interpret your result.
3. A sample of CaCl2 weighing 1.378 g was
𝐶𝐴𝐶𝑂3 = 40(1) + 12 (1) + 16 (3) dissolved in water and diluted to 250 mL. 50
= 100 𝑔/𝑚𝑜𝑙 mL of this solution was titrated with 38.2 mL
of 0.048 M disodium edentate. If each mL of
0.01 𝑚𝑜𝑙 𝐸𝐷𝑇𝐴 100 𝑔 1000 𝑚𝑔 0.05 M disodium acetate is equivalent to
𝑚𝑔 𝑜𝑓 𝐶𝐴𝐶𝑂3 = 40 𝑚𝐿 𝑥 𝑥 𝑥
1000 𝑚𝐿 1 𝑚𝑜𝑙 1𝑔 7.351 mg of 𝐶𝑎𝐶𝑙2 • 2𝐻2 𝑂. What is the
= 40 𝑚𝑔 𝑜𝑓 𝐶𝐴𝐶𝑂3 𝑖𝑛 𝑤𝑎𝑡𝑒𝑟 percentage purity of 𝐶𝑎𝐶𝑙2 • 2𝐻2 𝑂? USP
1𝐿 specs: 99-107%
50 𝑚𝐿 𝑥 = 0.050 𝐿
1000 𝑚𝐿
Formula 1:
40 𝑚𝑔 𝑉 𝑥 𝑁 𝑥 𝑚𝐸𝑞
𝑝𝑝𝑚 = % 𝑝𝑢𝑟𝑖𝑡𝑦 = 𝑥 100
0.050 𝐿
𝑝𝑝𝑚 𝑤𝑡
= 𝟖𝟎𝟎 𝒎𝒈/𝑳 𝒕𝒐𝒕𝒂𝒍 𝒉𝒂𝒓𝒅𝒏𝒆𝒔𝒔, 𝒘𝒉𝒄𝒉 𝒄𝒐𝒏𝒄𝒍𝒖𝒅𝒆𝒔 𝒕𝒐 𝒃𝒆 𝒖𝒏𝒅𝒆𝒓 𝒗𝒆𝒓𝒚 𝒉𝒂𝒓𝒅 𝒘𝒂𝒕𝒆𝒓 Formula 2:
𝐿 𝑜𝑓 𝑡𝑖𝑡𝑟𝑎𝑛𝑡 𝑥 𝑀 𝑥 𝑀𝑊
2. A 50 mL water sample was titrated with % 𝑝𝑢𝑟𝑖𝑡𝑦 = 𝑥 100
𝑤𝑡
32.50 mL of disodium edentate. 20.65 mL Formula 3:
of this EDTA was used to titrate 25 mL of a 𝑡𝑖𝑡𝑒𝑟 𝑥 𝑚𝐿
% 𝑝𝑢𝑟𝑖𝑡𝑦 = 𝑥 100
calcium carbonate solution. A 0.2155 g of 𝑤𝑡
pure calcium carbonate was acidified and
 0.0101 𝑚𝑜𝑙 𝐸𝐷𝑇𝐴 84 𝑔 1000 𝑚𝑔
𝑚𝑔 𝑜𝑓 𝑀𝑔𝐶𝑂3 (2𝑛𝑑) = 3.7 mL 𝑥 𝑥 𝑥
1000 𝑚𝐿 1 𝑚𝑜𝑙 1𝑔
𝐶𝑎𝐶𝑙2 • 2𝐻2 𝑂 = 40 (1) + 35 (2) + 1(4) + 16(2) = 3.1391 𝑚𝑔 𝑜𝑓 𝑀𝑔𝐶𝑂3 𝑖𝑛 𝑤𝑎𝑡𝑒𝑟
= 146 𝑔/𝑚𝑜𝑙
3.1391 𝑚𝑔
1.378 𝑔 𝑝𝑝𝑚 =
𝑥 50 𝑚𝐿 = 0.2756 𝑔 𝑜𝑓 𝐶𝑎𝐶𝑙2 0.020 𝐿
250 𝑚𝐿 𝑝𝑝𝑚 = 𝟏𝟓𝟔 𝒎𝒈/𝑳 𝒘𝒉𝒊𝒄𝒉 𝒄𝒐𝒏𝒄𝒍𝒖𝒅𝒆𝒔 𝒕𝒐 𝒉𝒂𝒓𝒅 𝒘𝒂𝒕𝒆𝒓

0.0382 𝐿 𝑥 0.048 𝑀 𝑥 146 𝑔/𝑚𝑜𝑙 5. Calculate the calcium carbonate content of a

% 𝐶𝑎𝐶𝑙2 • 2𝐻2 𝑂 = 𝑥 100
0.2756 𝑔 sample chalk weighing 0.2545 g and
%𝐶𝑎𝐶𝑙2 • 2𝐻2 𝑂 = 𝟗𝟕. 𝟏𝟒 % 𝒐𝒇 𝑪𝒂𝑪𝒍𝟐 • 𝟐𝑯𝟐 𝑶 consuming 26.67 mL of 0.1150 M EDTA
solution in titration

4. A 20 ml water sample was titrated with 3.50 𝐶𝑎𝐶𝑂3 = 40(1) + 12 (1) + 16 (3)
mL of disodium edentate. 8.56 mL of this = 100 𝑔/𝑚𝑜𝑙
EDTA was used to titrate 15 mL of a calcium
carbonate solution. A 0.145 g of pure
calcium carbonate was acifidied and 1𝐿
dissolved in 250 mL of a solvent. Another 20 26.67 𝑚𝐿 𝑥 = 0.027 𝐿
1000 𝑚𝐿
mL portion of the water sample was treated
with K2C2O4 and the resulting mixture 𝐿 𝑜𝑓 𝑡𝑖𝑡𝑟𝑎𝑛𝑡 𝑥 𝑀 𝑥 𝑀𝑊
% 𝑝𝑢𝑟𝑖𝑡𝑦 = 𝑥 100
consumed 3.7 mL of EDTA. Find the 𝑤𝑡
hardness in ppm in terms of magnesium 0.027 𝐿 𝑥 0.1150 M 𝑥 100 𝑔/𝑚𝑜𝑙
% 𝑝𝑢𝑟𝑖𝑡𝑦 = 𝑥 100
carbonate. Interpret your result. 0.2545 g
0.027 𝐿 𝑥 0.1150 M 𝑥 100 𝑔/𝑚𝑜𝑙
% 𝑝𝑢𝑟𝑖𝑡𝑦 = 𝑥 100
𝐶𝑎𝐶𝑂3 = 40(1) + 12 (1) + 16 (3) 0.2545 g
= 100 𝑔/𝑚𝑜𝑙 % 𝑝𝑢𝑟𝑖𝑡𝑦 = 𝟏𝟐𝟐. 𝟎𝟎 % 𝒐𝒇 𝑪𝒂𝑪𝒍
𝑀𝑔𝐶𝑂3 = 24(1) + 12 (1) + 16 (3)
= 84 𝑔/𝑚𝑜𝑙 6. How many grams of disodium EDTA acetate
or 𝐶10 𝐻14 𝑁2 𝑁𝑎2 𝑂8 • 2𝐻𝑂 is required to
0.145 g prepare 250 mL of a 0.025 M solution?
𝑥 15 𝑚𝐿 = 0.0087 𝑔 𝑜𝑓 𝐶𝐴𝐶𝑂3
250 𝑚𝐿 What would be the titer of this solution in
terms of 𝐶𝑎𝐶𝑙2 • 2𝐻2 𝑂, 𝑀𝑔𝑆𝑂4, 𝑎𝑛𝑑 𝑍𝑛𝐶𝑙2?
1L
8.56 𝑚𝐿 𝑥 = 0.0086 𝐿 𝑜𝑓 𝐸𝐷𝑇𝐴
1000 𝑚𝐿 𝑤𝑡
𝑀=
𝑀𝑊 𝑥 𝐿
𝑀 (𝑀𝑊)(𝐿) = 𝑤𝑡
𝑤𝑡
𝑀=
𝑀𝑊 𝑥 𝐿
0.0087 𝑔 (0.025 M) (371)(0.250 𝐿) = 𝑤𝑡
𝑀=
100 𝑔/𝑚𝑜𝑙 𝑥 0.0086 𝐿 𝟐. 𝟑𝟏𝟖𝟖 𝒈 𝒐𝒇 𝑬𝑫𝑻𝑨 𝒂𝒄𝒆𝒕𝒂𝒕𝒆 = 𝑤𝑡
𝑀 = 0.0101 𝑀 𝑜𝑟 𝑚𝑜𝑙/𝐿 𝑜𝑓 𝐸𝐷𝑇𝐴
𝑡𝑖𝑡𝑒𝑟 = 𝑀 (𝑀𝑊 )(0,001 𝐿)
0.0101 𝑚𝑜𝑙 𝐸𝐷𝑇𝐴 84 𝑔 1000 𝑚𝑔
𝑚𝑔 𝑜𝑓 𝑀𝑔𝐶𝑂3 (1𝑠𝑡) = 3.50 mL 𝑥 𝑥 𝑥 𝑡𝑖𝑡𝑒𝑟 = 0.025 𝑀 (146 𝑔/𝑚𝑜𝑙)(0,001 𝐿)
1000 𝑚𝐿 1 𝑚𝑜𝑙 1𝑔
= 2.9694 𝑚𝑔 𝑜𝑓 𝑀𝑔𝐶𝑂3 𝑖𝑛 𝑤𝑎𝑡𝑒𝑟 𝑡𝑖𝑡𝑒𝑟 = 𝟑. 𝟔𝟓 𝒎𝒈/𝒎𝑳 𝒐𝒇 𝑪𝒂𝑪𝒍𝟐 • 𝟐𝑯𝟐 𝑶

1𝐿 𝑡𝑖𝑡𝑒𝑟 = 0.025 𝑀 (120 𝑔/𝑚𝑜𝑙)(0,001 𝐿)

20 𝑚𝐿 𝑥 = 0.020 𝐿 𝑜𝑓 𝑤𝑎𝑡𝑒𝑟 𝑡𝑖𝑡𝑒𝑟 = 𝟑 𝒎𝒈/𝒎𝑳 𝒐𝒇 𝑴𝒈𝑺𝑶𝟒
1000 𝑚𝐿

2.9694 𝑚𝑔 𝑡𝑖𝑡𝑒𝑟 = 0.025 𝑀 (135 𝑔/𝑚𝑜𝑙)(0,001 𝐿)

𝑝𝑝𝑚 = 𝑡𝑖𝑡𝑒𝑟 = 𝟑. 𝟑𝟕𝟓 𝒎𝒈/𝒎𝑳 𝒐𝒇 𝒁𝒏𝑪𝒍𝟐
0.020 𝐿
𝑝𝑝𝑚 = 𝟏𝟒𝟖. 𝟒𝟕 𝒎𝒈/𝑳 𝒘𝒉𝒊𝒄𝒉 𝒄𝒐𝒏𝒄𝒍𝒖𝒅𝒆𝒔 𝒕𝒐 𝒉𝒂𝒓𝒅 𝒘𝒂𝒕𝒆𝒓

7. A 200 mg sample of pure calcium carbonate

was acidified and dissolved in 500 mL of
solution. A 50 mL sample required 25 mL of
an EDTA solution for titration. Find the
molarity of the EDTA solution.

𝐶𝑎𝐶𝑂3 = 40(1) + 12 (1) + 16 (3)

= 100 𝑔/𝑚𝑜𝑙

0.2 g
𝑥 50 𝑚𝐿 = 0.02 𝑔 𝑜𝑓 𝐶𝐴𝐶𝑂3
500 𝑚𝐿
𝑤𝑡
𝑀=
𝑀𝑊 𝑥 𝐿
0.02 𝑔
𝑀=
100 𝑔/𝑚𝑜𝑙 𝑥 0.025 𝐿
𝑀 = 𝟎. 𝟎𝟎𝟖𝟎 𝑴 𝒐𝒇 𝑬𝑫𝑻𝑨 𝒔𝒐𝒍𝒖𝒕𝒊𝒐𝒏
 PHAN111LEC_WEEK 9 𝐹2 + 2𝑒 − = 2𝐹; 𝑜𝑥𝑖𝑑𝑖𝑧𝑖𝑛𝑔 𝑎𝑔𝑒𝑛𝑡

Oxidation-Reduction Titration
• Wherein oxidation states of a certain atoms
change; relies on the oxidation number of
substances
• Electrons are transferred between reactants
• Simplest type is the direct combination of
elements
Ex.
𝑀𝑔0 + 𝑂2 0 = 𝑀𝑔2+ 𝑂 −2

−2
𝑍𝑛0 + 𝐻2 +1 𝑆 −8 𝑂4 = 𝑍𝑛+2 𝑆 −8 𝑂4 −2 + 𝐻2 0
From 𝑍𝑛0 to 𝑍𝑛+2 = reducing agent, underwent
oxidation; 2 electrons loss
From 𝐻2 +1 to 𝐻2 0 = oxidizing agent, underwent
reduction; 2 electrons gained

• Importance:
o Antiseptic effect
o Effects on hair treatment
o Black and white photography
o Breath alcohol analyzer

Principle and Concepts Standard Solutions for REDOX

a. Faraday’s Law – “change of one is equal to • Strong Oxidizing Agents
the gain or loss of 96,500C of electricity for o Potassium Permanganate ; 𝐾𝑀𝑛𝑂4
each formula weight of element or group of o Ceric Sulfate ; 𝐶𝑒𝐻2 𝑂4 𝑆
elements involved.” o Iodine
• Reducing Agent o Bromine
o Loses electrons o Potassium Iodate ; 𝐾𝐼𝑂3
o Causes the reduction (i.e. gain of • Strong Reducing Agents
positive charge) o Oxalic acid ; 𝐶2 𝐻2 𝑂4
o VILEORA = Valence Increase Loses o Ferrous sulfate ; 𝐹𝑒𝑆𝑂4
Electrons Oxidation Reducing Agent o Sodium Thiosulfate ; 𝑁𝑎2 𝑆2 𝑂3
Ex.
𝐹𝑒 +2 = 𝐹𝑒 +3 + 𝑒 IMPORTANT COMBINATIONS:
• Oxidizing Agent Potassium Permanganate and Oxalic Acid
o Gains electrons Ceric Sulfate and Ferrous Sulfate
o Causes the oxidation (i.e. loss of Iodine and Sodium Thiosulfate
positive charge)
o VaDGEORA = Valence Decrease
Gain Electrons Reduction Oxidizing Rules in Oxidation Reaction
Agent 1. Oxidation state of an element in a free state
or combined form is equal to zero
Ex. 2. Oxidation state of H+ in a compound is +1
𝐶𝑒 +4 = 𝐶𝑒 +3 + 𝑒 except in combination with metals which is -
• Half Reactions 1
Ex.
𝐻2 0 + 𝐹2 0 = 2𝐻+1 𝐹 −1 𝑁𝑎 +1 𝐻−1
𝐶𝑎 +2 𝐻2 −1
𝐻2 = 2𝐻 + 2𝑒 − ; 𝑟𝑒𝑑𝑢𝑐𝑖𝑛𝑔 𝑎𝑔𝑒𝑛𝑡 𝐴𝑙 +3 𝐻3 −1

3. Oxidation state of oxygen in a compound is -
2 except in peroxides which is -1
Ex.
𝐻2 +1 𝑂2 −1
4. Group IA – oxidation state is +1
Group IIA – oxidation state is +2
Halogens – oxidation state is -1 but positive
with oxygen
Flourine is always -1
Ex.
−1
𝐶𝑙+3 𝑂2 −2 ; "𝑐ℎ𝑙𝑜𝑟𝑖𝑡𝑒"
𝐶𝑙𝑂3 ; "𝑐ℎ𝑙𝑜𝑟𝑎𝑡𝑒"
𝐶𝑙𝑂; "ℎ𝑦𝑝𝑜𝑐ℎ𝑙𝑜𝑟𝑖𝑡𝑒"
𝐶𝑙 +7 𝑂4 −2 ; "𝑝𝑒𝑟𝑐ℎ𝑙𝑜𝑟𝑎𝑡𝑒"
5. For monoatomic compounds, the charge is
its oxidation state
6. The algebraic sum of the oxidation state of a
neutral compound is equal to zero
Ex.
𝑁𝑎 +1 𝐶𝑙−1
𝐾 +1 𝐶𝑙−1
𝐾 𝑀𝑛+7 𝑂4 −2
+1
𝑁𝑎2 +1 𝐶2 +3 𝑂4 −2
𝐶𝑎 +2 𝐶 +3 𝑂3 −2
𝐻2 +1 𝑆 +6 𝑂4 −2
𝐻2 +1 𝑂2 −1
𝐴𝑔+1 𝑁 +5 𝑂3 −2
𝑀𝑔+2 𝑂−2
𝑁𝑎2 +2 𝐶 +2 𝑂3 −2
𝐾 +1 𝐻+1 𝐶 +4 𝑂3 −2
𝑍𝑛+2 𝑆 +6 𝑂4 −2
7. The oxidation state of a polyatomic ions is
equal to the ionic charge
Ex.
𝐶2+6 𝑂4 −2 ; "𝑐𝑎𝑟𝑏𝑜𝑛 𝑜𝑥𝑎𝑙𝑎𝑡𝑒"
𝐻+1 𝐶 +4 𝑂3 −2 ; "𝑏𝑖𝑐𝑎𝑟𝑏𝑜𝑛𝑎𝑡𝑒"
𝐶𝑟2 +6 𝑂7 −2 ; "𝑑𝑖𝑐ℎ𝑟𝑜𝑚𝑎𝑡𝑒"
𝑃 +5 𝑂4 −2 ; "𝑝ℎ𝑜𝑠𝑝ℎ𝑎𝑡𝑒"
𝑆 +6 𝑂4 −2 ; "𝑠𝑢𝑙𝑓𝑎𝑡𝑒"
𝐶 +4 𝑂3 −2 ; "𝑐𝑎𝑟𝑏𝑜𝑛𝑎𝑡𝑒"
−2
𝐶𝑟 +6 𝑂4 −2 ; "𝑐ℎ𝑟𝑜𝑚𝑎𝑡𝑒"
𝑆2 +2 𝑂3 −2 ; "𝑡ℎ𝑖𝑜𝑠𝑢𝑙𝑓𝑎𝑡𝑒"
𝑀𝑛 +7 𝑂4 −2 ; "𝑝𝑒𝑟𝑚𝑎𝑛𝑔𝑎𝑛𝑎𝑡𝑒"
𝐶6 +1 𝐻5 +1 𝑂7 −2 ; "𝑐𝑖𝑡𝑟𝑎𝑡𝑒"
TYPES OF REDOX TITRATION
A. Permanganometry
a. Uses KMnO4 VS; characteristics:
valuable and powerful oxidizing
agent used for the titration of iron
i. can be standardized easily
ii. can retain its concentration
for a long period of time; if
properly kept, otherwise it
can lose concentration from
purple to brown (useless)
iii. The reaction of
permanganate in solution is
rapid
iv. Can serve as an indicator in
titration
b. Primary standard: Sodium Oxalate;
Oxalic acid is most effective chemical
substance in removing KMnO4 stains
c. Excess KMnO4 imparts pink color
Types of Titration Example Analytes
Direct Hydrogen Peroxide
Indirect Malic acid in Cherry
Juice
Residual Sodium nitrite
d. 2 Types of Residual Titration
i. Titration in which excess of
standard KMnO4 is employed
to oxidize a substance, and
the amount in excess is
determined by the reduction
with:
1. Standard oxalic acid
2. Excess ferrous
ammonium sulfate
and back titrated with
potassium
permanganate
ii. Titration in which an excess
of standard oxalic acid
solution is added to the
substance and the excess
oxalic acid is titrated with
standard KMnO4.
B. Cerimetry
a. VS: Ceric Sulfate and Ferrous
Ammonium sulfate (for residual)
b. Indicators: orthophenanthroline-
ferrrous sulfate; red in reducing
agents, pale green or blue in
oxidizing agents
c. Analytes: ferrous sulfate syrup and
tablets, menadione tablets,
menadione sodium bisulfite, and
menadione sodium bisulfate
injection, ferrous carbonate mass and
pills.
 d. Ceric sulfate is a powerful oxidizing
agent that can be used in titrations
of organic substances; should not be
boiled with HCl and should only be
conducted only in acid media to
prevent hydrolysis
e. Solutions in this type are less
susceptible to decomposition and it
can be used in the titration of
ferrous ion in the presence of
chloride at room temp.
f. Advantages
i. Stable over prolonged
periods of time even on
boiling;
ii. React quantitatively with
oxalate or arsenic ion
iii. No intermediate products are
formed in the reduction of
ceric to cerium
iv. Maybe employed in the
determination of reducing
agent in the presence of high
concentration HCl
v. Not too highly
colored(colorless) to obstruct
the vision when reading the
meniscus
Ex.
Assay of Ferrous Sulfate Tablets (Direct Titration)
• 20 tablets are weighed, dissolved in a
mixture of 20 mL diluted sulfuric acid and 80
mL of boiled and cooled water and filtered.
Orthophenanthroline T.S. is added and
titrated with ceric sulfate. Each mL of 0.1 N
ceric sulfate is equivalent to 27.8 mg of
𝐹𝑒𝑆𝑂4 • 7𝐻2 𝑂
Assay of Potassium Chloride in Ringer’s solution and
injection (Residual assay)
• The principle consists in precipitation of the
sample with sodium cobaltinitrite in the
presence of alcohol forming dipotassium
sodiumcobalnitrite. The precipitate is
washed with 70% alcohol, centrifuged,
decanted, and allow to drain and dried to 80
degC. When the dried precipitate is treated
with a measured excess of standard ceric
sulfate solution and 18 N sulfuric acid,
heated until the precipitate has disappeared.
The mixture is cooled to room temperature
and the excess of ceric sulfate is titrated
with standard ferrous ammonium sulfate
with orthophenanthroline T.S. as indicator
C. Iodimetry
a. VS: Iodine as oxidizing agent; iodine
solutions and sodium thiosulfate in
neutral or slightly acidic medium
b. Direct reaction
c. Indicator: In colorless, iodine is
sufficient; Freshly prepared Starch
solution is most commonly used;
Carbon tetrachloride and chloroform
may be used
Free Iodine Solution is used; difficult to prepare
because iodine is less soluble in water; ergo it was
made with the use of KI
𝐾𝐼 + 𝐼2 = 𝐾𝐼3
d. Analytes: Pharmaceutical solutions
of arsenites, trivalent antimony
compounds, thiosulfates, sulfites,
mercurous compounds, ascorbic acid,
methenamine. Sodium sulfite,
calomel, caffeine in APC tablets, and
yellow mercurous iodide
Types of Reaction Example Analytes
Direct Ascorbic acid,
Antimony potassium
tartrate
Residual w/ 𝑁𝑎2 𝑆2 𝑂3 Calomel, antipyrine
D. Iodometry
a. Titration in which an equivalent
amount of iodine from potassium
iodide is liberated using Sodium
thiosulfate
b. Indirect reaction
c. Indicator: iodine is sufficient with a
small amount of carbon tetrachloride
d. Never carried out in strongly basic
solution
Types of Reaction Example Analytes
Direct CuSO4
Residual Phenol, resorcinol, lead
oxide
REDOX Method with 0.1 N Bromine
• A.k.a. Koppesschar’s Solution
• used in assays of aniline, phenol and
resorcinol
 • Bromine is liberated when solution is 2.) What volume of 0.1225 N sodium hydroxide
acidified would be required in a titration of a 0.1065
• VS does not contain bromine but rather an g sample of oxalic acid if a 0.1126 g sample
equivalent amount of potassium bromate of the oxalic acid required 24.65 mL of
and excess potassium bromide 0.0965 N potassium permanganate in a
titration?
Redox Reaction with Potassium Iodate
• Potassium iodate is used as oxidizing agent 𝐻2 𝐶2 𝑂4 + 𝑁𝑎𝑂𝐻 → 𝑁𝑎2 𝐶2 𝑂4 + 𝐻2 𝑂
with iodides, arsenites, and other reducing
agents 𝐻2 𝐶2 𝑂4 = 1(2) + 12(2) + 16(4)
• Depends upon the formation of iodine 90
=
monochloride in strong HCl solution 2(1000)
= 0.045 𝑔/𝑚𝑜𝑙
Practice
1.) A 0.2295 g of sodium oxalate (97.8%)
required 35.12 mL of a potassium 𝑤𝑡
𝑁=
permanganate solution in a titration. What 𝑚𝐿 𝑥 𝑚𝐸𝑞
was the normality of the permanganate 𝑁 𝑥 𝑚𝐿 𝑥 𝑚𝐸𝑞 𝑤𝑡
= .
solution? 𝑁 𝑥 𝑚𝐸𝑞 𝑁 𝑥 𝑚𝐸𝑞
𝑤𝑡
𝑚𝐿 =
𝑁𝑎2 𝐶2 𝑂4 + 𝐾𝑀𝑛𝑂4 + 𝐻2 𝑆𝑂4 𝑁 𝑥 𝑚𝐸𝑞
→ 𝑀𝑛𝑆𝑂4 + 𝑁𝑎2 𝑆𝑂4 + 𝐾2 𝑆𝑂4 + 𝐶𝑂2
+ 𝐻2 𝑂
0.1065 g
𝑚𝐿 =
* find the byproduct with similar molecules that 0.1225 N 𝑥 0.045 𝑔/𝑚𝑜𝑙
depicts a change in oxidation; usually find the change 𝑚𝐿 = 𝟏𝟗. 𝟑𝟐 𝒎𝑳 𝒐𝒇 𝑵𝒂𝑶𝑯
in the middle atom

𝑁𝑎2 +1 𝐶2 +2 𝑂4 −2 → 𝐶 +4 𝑂2 −2 3.) What volume of 0.1225 N sodium hydroxide

* Half Reaction Formula: would be required in a titration of a 0.1065
𝐶2 +3 → 𝐶 +4 + 2𝑒 − ; 𝑟𝑒𝑑𝑢𝑐𝑖𝑛𝑔 𝑎𝑔𝑒𝑛𝑡 g sample of sodium oxalate if a 0.1126 g
The factor would be 2 since 2 electrons are lost sample of the sodium oxalate required 24.65
mL of 0.0965 N potassium permanganate in
a titration?
𝑁𝑎2 +1 𝐶2 +2 𝑂4 −2 = 23(2) + 12(2) + 16(4)
134 𝑁𝑎2 +1 𝐶2 +2 𝑂4 −2 → 𝐶 +4 𝑂2 −2
=
2(1000)
= 0.067 𝑔/𝑚𝐸𝑞
𝑁𝑎2 +1 𝐶2 +2 𝑂4 −2 = 23(2) + 12(2) + 16(4)
𝑚𝐿 𝑥 𝑁 𝑥 𝑚𝐸𝑞 134
% 𝑝𝑢𝑟𝑖𝑡𝑦 = 𝑥100 =
𝑤𝑡. 2(1000)
% 𝑝𝑢𝑟𝑖𝑡𝑦 𝑚𝐿 𝑥 𝑁 𝑥 𝑚𝐸𝑞 = 0.067 𝑔/𝑚𝐸𝑞
=
100 𝑤𝑡.
𝑚𝐿 𝑥 𝑁 𝑥 𝑚𝐸𝑞 𝑤𝑡
%𝑝𝑢𝑟𝑖𝑡𝑦 (𝑤𝑡. ) = 𝑁=
𝑚𝐿 𝑥 𝑚𝐸𝑞. 𝑚𝐿 𝑥 𝑚𝐸𝑞
%𝑝𝑢𝑟𝑖𝑡𝑦 (𝑤𝑡. ) 𝑚𝐿 𝑥 𝑁 𝑥 𝑚𝐸𝑞 𝑁 𝑥 𝑚𝐿 𝑥 𝑚𝐸𝑞 𝑤𝑡
= =
𝑚𝐿 𝑥 𝑚𝐸𝑞 𝑚𝐿 𝑥 𝑚𝐸𝑞 𝑁 𝑥 𝑚𝐸𝑞 𝑁 𝑥 𝑚𝐸𝑞
%𝑝𝑢𝑟𝑖𝑡𝑦 (𝑤𝑡. ) 𝑤𝑡
𝑁= 𝑚𝐿 = .
𝑚𝐿 𝑥 𝑚𝐸𝑞 𝑁 𝑥 𝑚𝐸𝑞

0.978 (0.2295 g) 0.1065 g

𝑁= 𝑚𝐿 =
35.12 mL 𝑥 0.067 𝑔/𝑚𝐸𝑞 0.1225 N 𝑥 0.067 𝑔/𝑚𝐸𝑞
𝑁 = 𝟎. 𝟎𝟗𝟓𝟒 𝑵 𝒐𝒇 𝑲𝑴𝒏𝑶𝟒 𝑚𝐿 = 𝟏𝟐. 𝟗𝟖 𝒎𝑳 𝒐𝒇 𝑵𝒂𝑶𝑯
 [(𝑁1 𝑉1 ) − (𝑁2 𝑉2 )] 𝑥 𝑚𝐸𝑞
%= 𝑥100
4.) P. 162 from book: A 2 mL sample of 𝑤𝑡.
hydrogen peroxide solution required 8.5 mL %=
[(0.1𝑁 𝑥 54.58 𝑚𝐿) − (0.0975 𝑁 𝑥 25 𝑚𝐿)] 𝑥 0.0345 𝑔/𝑚𝑜𝑙
𝑥100
0.11 𝑔
of a permanganate solution in titration. If
% = 𝟎. 𝟗𝟒% 𝒐𝒇 𝑵𝒂𝑵𝑶𝟑
each mL of the permanganate solution is
equivalent to 0.007294 g of Fe. What % w/v
6.) Twenty tablets of ferrous sulfate weighed
of hydrogen peroxide was in the sample?
5.985 g and a powdered sample of 0.298 g
was titrated consuming 5.85 mL of 0.1458 N
𝐻2 +1 𝑂2 −1 → 𝑂2 0 ; 𝑂2 + 2𝑒 − of ceric sulfate solution. Each mL of 0.1 N of
ceric sulfate is equivalent to 27.80 mg of
𝐻2 𝑂2 = 1(2) + 16(2)
ferrous sulfate. What is the amount of
34
= ferrous sulfate per tablet? Calculate thel
2(1000) percentage label claim if each tablet is 250
= 0.017 𝑔/𝑚𝐸𝑞
mg.
𝐹𝑒 = 56 5.985 𝑔 𝑥
56 𝑥 = 0.2993 𝑔 𝑜𝑟 299.25 𝑚𝑔
𝐹𝑒 = 20 𝑡𝑎𝑏𝑙𝑒𝑡𝑠 1 𝑡𝑎𝑏𝑙𝑒𝑡
1(1000)
𝐹𝑒 = 0.056 𝑔/𝑚𝐸𝑞 * If substance with a given titer value is similar to the
substance assayed, there is no need to make the
𝑡𝑖𝑡𝑒𝑟 = 𝑁 (𝑚𝐸𝑞) reaction as mEq can already be computed from the
𝑡𝑖𝑡𝑒𝑟 𝑁 (𝑚𝐸𝑞)
= titer formula
𝑚𝐸𝑞 𝑚𝐸𝑞
𝑡𝑖𝑡𝑒𝑟 𝑡𝑖𝑡𝑒𝑟 = 𝑁 (𝑚𝐸𝑞)
𝑁=
𝑚𝐸𝑞 𝑡𝑖𝑡𝑒𝑟 𝑁 (𝑚𝐸𝑞)
=
𝑁 𝑁
0.007294 g 𝑡𝑖𝑡𝑒𝑟
𝑁= 𝑚𝐸𝑞 =
0.056 𝑔/𝑚𝑜𝑙 𝑁
𝑁 = 0.1303 𝑁 𝑜𝑓 𝐾𝑀𝑛𝑂4
0.0278 𝑔
𝑚𝐿 𝑥 𝑁 𝑥 𝑚𝐸𝑞 𝑚𝐸𝑞 =
0.1 N
% 𝑝𝑢𝑟𝑖𝑡𝑦 = 𝑥100 𝑚𝐸𝑞 = 0.278 𝑔/𝑚𝐸𝑞
𝑤𝑡.
8.5 mL 𝑥 0.1303 𝑁 𝑥 0.017 𝑔/𝑚𝑜𝑙
% 𝑝𝑢𝑟𝑖𝑡𝑦 = 𝑥100 𝑚𝐿 𝑥 𝑁 𝑥 𝑚𝐸𝑞
2 mL 𝑚𝑔/𝑡𝑎𝑏 = 𝑥 𝑚𝑔/𝑡𝑎𝑏
% 𝑝𝑢𝑟𝑖𝑡𝑦 = 𝟗𝟒. 𝟏𝟒% 𝒘/𝒗 𝒐𝒇 𝑯𝟐 𝑶𝟐 𝑤𝑡
5.85 mL 𝑥 0.1458 N 𝑥 0.278 𝑔/𝑚𝐸𝑞
𝑚𝑔/𝑡𝑎𝑏 = 𝑥 299.25 𝑚𝑔
5.) p. 169, no. 2: % of sodium nitrite in 0.298 g
/𝑡𝑎𝑏
potassium permanganate 𝑚𝑔
= 𝟐𝟑𝟖. 𝟏𝟏 𝒎𝒈/𝒕𝒂𝒃 𝒐𝒇 𝑭𝒆𝑺𝑶𝟒
𝑡𝑎𝑏
𝑁𝑎 +1 𝑁 +3 02 −2 → 𝐻+1 𝑁 +5 𝑂3 −2

𝑁𝑎𝑁𝑂2 = 23(1) + 14(1) + 16(2) 𝑒𝑥𝑝𝑒𝑟𝑖𝑚𝑒𝑛𝑡𝑎𝑙 𝑣𝑎𝑙𝑢𝑒

69 %𝑙𝑎𝑏𝑒𝑙 = 𝑥100
= 𝑡ℎ𝑒𝑜𝑟𝑒𝑡𝑖𝑐𝑎𝑙 𝑣𝑎𝑙𝑢𝑒
2(1000) 238.11 𝑚𝑔
= 0.0345 𝑔/𝑚𝐸𝑞 %𝑙𝑎𝑏𝑒𝑙 = 𝑥100
250 mg
%𝑙𝑎𝑏𝑒𝑙 = 𝟗𝟓. 𝟐𝟒% 𝒐𝒇 𝑭𝒆𝑺𝑶𝟒
1.100 𝑔
𝑥 10 𝑚𝐿 = 0.11 𝑔
100 𝑚𝐿 7.) Twenty tablets of ascorbic acid weighed
4.2500 g and a powdered sample of 0.3075
𝑇𝑜𝑡𝑎𝑙 𝑚𝐿 𝑜𝑓 𝐾𝑀𝑛𝑂4 = 50 𝑚𝐿 + 4.50 𝑚𝐿 g was titrated consuming 21.5 mL of 0.1085
= 54.58 𝑚𝐿 𝑜𝑓 𝐾𝑀𝑛𝑂4 N iodine solution. Each mL of 0.1 N iodine is
equivalent to 8.80 mg of ascorbic acid. What
is the amount of ascorbic acid per dose of
two tablets?
 5.985 𝑔 𝑥
𝑥 = 0.2125 𝑔 𝑜𝑟 212.5 𝑚𝑔
20 𝑡𝑎𝑏𝑙𝑒𝑡𝑠 1 𝑡𝑎𝑏𝑙𝑒𝑡

𝑡𝑖𝑡𝑒𝑟 𝑁 (𝑚𝐸𝑞)
=
𝑁 𝑁
𝑡𝑖𝑡𝑒𝑟
𝑚𝐸𝑞 =
𝑁

0.0088 𝑔
𝑚𝐸𝑞 =
0.1 N
𝑚𝐸𝑞 = 0.088 𝑔/𝑚𝐸𝑞

𝑚𝐿 𝑥 𝑁 𝑥 𝑚𝐸𝑞
𝑚𝑔/𝑡𝑎𝑏 = 𝑥 𝑚𝑔/𝑡𝑎𝑏
𝑤𝑡
21.5 mL 𝑥 0.1085 N 𝑥 0.088 𝑔/𝑚𝐸𝑞
𝑚𝑔/𝑡𝑎𝑏 = 𝑥 212.5 𝑚𝑔/𝑡𝑎𝑏
0.3075 g
𝑚𝑔/𝑡𝑎𝑏 = 141.86 𝑚𝑔/𝑡𝑎𝑏 𝑜𝑓 𝑎𝑠𝑐𝑜𝑟𝑏𝑖𝑐 𝑎𝑐𝑖𝑑

𝑑𝑜𝑠𝑒 𝑜𝑓 2 𝑡𝑎𝑏𝑠 = 141.86 𝑚𝑔/𝑡𝑎𝑏 (2)

𝑑𝑜𝑠𝑒 𝑜𝑓 2 𝑡𝑎𝑏𝑠 = 𝟐𝟖𝟑. 𝟕𝟐 𝒎𝒈/𝟐 𝒕𝒂𝒃𝒔 𝒐𝒇 𝒂𝒔𝒄𝒐𝒓𝒃𝒊𝒄 𝒂𝒄𝒊𝒅
 PHAN111LEC_WEEK 10
Gravimetric Method
• Consists of isolating from the sample the
constituent to be determined in its pure
state and weighing accurately
• Isolation may be carried out by:
o Precipitating the sought substance in
an insoluble form (most common)
o Depending on pure metal by
electrolysis (not commonly used in
pharmaceutical analysis)
o By converting the substance to a gas
which is absorbed in a suitable
reagent
Precipitation
• Low solubility; large particles; easily filtered;
pure and stable
• Laws Applied on Precipitation
o Solubility Product Principle
▪ If the ionic product exceeds
the solubility product
constant precipitation will
occur
o The Common Ion Effect
▪ If there is an excess of one
ion over the other, the
solubility of the precipitate
will decrease
o Law of Mass Action
▪ The rate of reaction is
directly proportional to the
product of the molecular
concentrations of the
reacting substance
▪ Velocity of reaction depends
on the molecular
concentrations of the
reactant
▪ At equilibrium, the products
is equal to reactants
• Isolation by precipitation involves:
o Weighing of appropriate quantity of
the sample
o Preparation of tared crucible where
precipitate is dried and weighed
o Bringing into solution of the
constituent to be determined,
separating it from substances that
may interfere in the process
o Precipitation of the constituent to be
determined
o Filtration and washing of the
precipitate to remove adhering or
absorbed substances
o Drying of the precipitate and
weighing it accurately
Ex.
Gravimetric Method by Precipitation Assay of
Sodium Sulfate
• Five hundred mg sample is dissolved in 150
mL of distilled water, 12 mL of conc. HCl is
added and heated to boiling. 20 mL of
barium chloride (precipitating agent) is
poured to the hot solution of the sample.
The precipitate formed is allowed to settle
and test for complete precipitation by
adding a few drops of barium chloride
solution. Cover the beaker with a watch
glass and digest first below boiling for one
hour. The supernatant liquid is decanted and
the precipitate is washed three times with
warm water. The residue is white. It is then
cooled and weighed.
Calculations
• Example:
o Bismuth carbonate is required to
yield on ignition not less than 90% of
𝐵𝑖2 𝑂3 . The percentage of the latter
may be obtained by simply dividing
the weight of the residue by the
weight of the sample and multiply by
100.
• Factor – commonly called as chemical
factor, calculation factor, conversion factor,
equivalent factor, or gravimetric factor;
defined as the weight of the constituent
determined or sought and is equivalent to
the unit weight of a given substance
𝑀𝑊 𝑜𝑓 𝑠𝑥.
𝐶𝐹 = .
𝑀𝑊 𝑜𝑓 𝑝𝑝𝑡.
𝑤𝑡. 𝑜𝑓 𝑝𝑝𝑡 𝑥 𝐶𝐹
%= 𝑥 100
𝑤𝑡. 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
Ex.
The chemical factor of 𝑁𝑎2 𝑆𝑂4 in 𝐵𝑎𝑆𝑂4 :
𝑀𝑊 𝑜𝑓 𝑠𝑥.
𝐶𝐹 = .
𝑀𝑊 𝑜𝑓 𝑝𝑝𝑡.
𝑁𝑎2 𝑆𝑂4 142.52
𝐶𝐹 = = = 𝟎. 𝟔𝟎𝟖𝟔
𝐵𝑎𝑆𝑂4 233.43
 = 233 𝑔/𝑚𝑜𝑙

Practice
1) A 0.3056 g sample of soluble chloride was 𝑀𝑊 𝑜𝑓 𝐴𝑙2 (𝑆𝑂4 )3
𝐶𝐹 = .
analyzed gravimetrically for Cl and 0.7265 g 𝑀𝑊 𝑜𝑓 𝐵𝑎𝑆𝑂4
of AgCl was obtained. Calculate the Cl and
NaCl contents of the sample, expressing * Identical elements between molecules should be equivalent
each in % w/w to each other; therefore, since there are 3 SO4 molecules in
Al2SO4, there should be 3 SO4 molecules as well in BaSO4
__𝐶𝑙 + 𝐴𝑔𝑁𝑂3 → 𝐴𝑔𝐶𝑙 ↓ + __𝑁𝑂3
𝑁𝑎𝐶𝑙 + 𝐴𝑔𝑁𝑂3 → 𝐴𝑔𝐶𝑙 + 𝑁𝑎𝑁𝑂3 𝑀𝑊 𝑜𝑓 𝐴𝑙2 (𝑆𝑂4 )3
𝐶𝐹 = .
𝑀𝑊 𝑜𝑓 3𝐵𝑎𝑆𝑂4
𝐶𝑙 = 35 𝑔/𝑚𝑜𝑙 342 𝑔/𝑚𝑜𝑙
𝐶𝐹 = .
3 𝑥 233 𝑔/𝑚𝑜𝑙
𝑁𝑎𝐶𝑙 = 23 (1) + 35 (1) 𝐶𝐹 = 𝟎. 𝟒𝟖𝟗𝟑
= 58 𝑔/𝑚𝑜𝑙
3) A precipitate of AgCl weighing 0.2432 g was
𝐴𝑔𝐶𝑙 = 108 (1) + 35 (1) obtained from 25 mL sample of HCl
= 143 𝑔/𝑚𝑜𝑙 solution. Calculate (a) HCl content of the
solution w/v, (b) molarity of the solution
𝑀𝑊 𝑜𝑓 𝐶𝑙
𝐶𝐹 = .
𝑀𝑊 𝑜𝑓 𝐴𝑔𝐶𝑙 𝐻𝐶𝑙 + 𝐴𝑔𝑁𝑂3 → 𝐴𝑔𝐶𝑙 + 𝐻𝑁𝑂3
35 𝑔/𝑚𝑜𝑙
𝐶𝐹 = .
143 𝑔/𝑚𝑜𝑙 𝐻𝐶𝑙 = 1(1) + 35(1)
𝐶𝐹 = 0.2448 = 36 𝑔/𝑚𝑜𝑙

𝐴𝑔𝐶𝑙 = 108 (1) + 35 (1)

𝑤𝑡. 𝑜𝑓 𝑝𝑝𝑡 𝑥 𝐶𝐹 = 143 𝑔/𝑚𝑜𝑙
%= 𝑥 100
𝑤𝑡. 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
0.7265 g 𝑥 0.2448
% 𝐶𝑙 = 𝑥 100 𝑀𝑊 𝑜𝑓 𝐻𝐶𝑙
0.3056 g 𝐶𝐹 = .
% = 𝟓𝟖. 𝟐𝟎% 𝒐𝒇 𝑪𝒍 𝑀𝑊 𝑜𝑓 𝐴𝑔𝐶𝑙
36 𝑔/𝑚𝑜𝑙
𝐶𝐹 = .
143 𝑔/𝑚𝑜𝑙
𝑀𝑊 𝑜𝑓 𝑁𝑎𝐶𝑙 𝐶𝐹 = 0.2517
𝐶𝐹 = .
𝑀𝑊 𝑜𝑓 𝐴𝑔𝐶𝑙
58 𝑔/𝑚𝑜𝑙
𝐶𝐹 = . 𝑤𝑡. 𝑜𝑓 𝑝𝑝𝑡 𝑥 𝐶𝐹
143 𝑔/𝑚𝑜𝑙 %= 𝑥 100
𝐶𝐹 = 0.4056 𝑤𝑡. 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
0.2432 g 𝑥 0.2517
% 𝐻𝐶𝑙 = 𝑥 100
𝑤𝑡. 𝑜𝑓 𝑝𝑝𝑡 𝑥 𝐶𝐹 25 mL
%= 𝑥 100 0.2432 g 𝑥 0.2517
𝑤𝑡. 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒 % 𝐻𝐶𝑙 = 𝑥 100
0.7265 g 𝑥 0.4056 25 mL
% 𝑁𝑎𝐶𝑙 = 𝑥 100 % 𝐻𝐶𝑙 = 𝟎. 𝟐𝟒% 𝒘/𝒗 𝒐𝒇 𝑯𝑪𝒍
0.3056 g
% 𝑁𝑎𝐶𝑙 = 𝟗𝟔. 𝟒𝟐% 𝒐𝒇 𝑵𝒂𝑪𝒍
𝑤𝑡
𝑀=
𝑀𝑊 𝑥 𝐿
2) Find the CF of Aluminum sulfate to which a 0.2432 g
precipitate of Barium sulfate was formed. 𝑀=
143 𝑔/𝑚𝑜𝑙 𝑥 0.025 𝐿
𝑀 = 𝟎. 𝟎𝟔𝟖𝟎 𝑴 𝒐𝒇 𝑯𝑪𝒍
𝐴𝑙2 (𝑆𝑂4 )3 = 27 (2) + 32 (3) + 16 (4 𝑥 3)
= 342 𝑔/𝑚𝑜𝑙 4) An unknown sample of a soluble sulfate
weighing 1.800 g yielded 0.9000 g of
𝐵𝑎𝑆𝑂4 = 137 (1) + 32 (1) + 16(4)
 Barium sulfate. Calculate the percentage of
sulfur in the unknown. If soluble sulfate and 𝑀𝑔𝑆𝑂4 = 23(1) + 32(1) + 16(4)
precipitate is barium sulfate, precipitating = 119 𝑔/𝑚𝑜𝑙
agent must be: SO4 + Ba_ to form BaSO4 +
___ 𝐵𝑎𝑆𝑂4 = 137(1) + 32(1) + 16 (4)
= 233 𝑔/𝑚𝑜𝑙
__𝑆𝑂4 + 𝐵𝑎𝐶𝑙2 → 𝐵𝑎𝑆𝑂4 ↓ + __𝐶𝑙
𝑀𝑊 𝑜𝑓 𝑀𝑔𝑆𝑂4
𝐶𝐹 = .
𝑆 = 32 𝑔/𝑚𝑜𝑙 𝑀𝑊 𝑜𝑓 𝐵𝑎𝑆𝑂4
119 𝑔/𝑚𝑜𝑙
𝐶𝐹 = .
𝐵𝑎𝑆𝑂4 = 137(1) + 32(1) + 16 (4) 233 𝑔/𝑚𝑜𝑙
= 233 𝑔/𝑚𝑜𝑙 𝐶𝐹 = 0.5107

𝑀𝑊 𝑜𝑓 𝑆 𝑤𝑡. 𝑜𝑓 𝑝𝑝𝑡 𝑥 𝐶𝐹
𝐶𝐹 = . %= 𝑥 100
𝑀𝑊 𝑜𝑓 𝐵𝑎𝑆𝑂4 𝑤𝑡. 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
32 𝑔/𝑚𝑜𝑙 0.9000 g 𝑥 0.5107
𝐶𝐹 = . %= 𝑥 100
233 𝑔/𝑚𝑜𝑙 1.800 g
𝐶𝐹 = 0.1373 % = 𝟐𝟓. 𝟓𝟒% 𝒐𝒇 𝑴𝒈𝑺𝑶𝟒

𝑤𝑡. 𝑜𝑓 𝑝𝑝𝑡 𝑥 𝐶𝐹
%= 𝑥 100
𝑤𝑡. 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒 𝐾2 𝑆𝑂4 + 𝐵𝑎𝐶𝑙2 → 𝐵𝑎𝑆𝑂4 ↓ +𝐾𝐶𝑙2
0.9000 g 𝑥 0.1373
%𝑆= 𝑥 100
1.800 g 𝐾2 𝑆𝑂4 = 39(2) + 32(1) + 16(4)
% 𝑆 = 𝟔. 𝟖𝟕% 𝒐𝒇 𝒔𝒖𝒍𝒇𝒖𝒓 = 174 𝑔/𝑚𝑜𝑙

5) Calculate the mercury bichloride content of 𝐵𝑎𝑆𝑂4 = 137(1) + 32(1) + 16 (4)

the sample if 0.2551 g of which yields = 233 𝑔/𝑚𝑜𝑙
0.1815 g of mercuric sulfide
𝑀𝑊 𝑜𝑓 𝐾2 𝑆𝑂4
𝐶𝐹 = .
𝐻𝑔𝐶𝑙2 = 201(1) + 35(2) 𝑀𝑊 𝑜𝑓 𝐵𝑎𝑆𝑂4
= 271 𝑔/𝑚𝑜𝑙 174 𝑔/𝑚𝑜𝑙
𝐶𝐹 = .
233 𝑔/𝑚𝑜𝑙
𝐻𝑔𝑆 = 201(1) + 32(1) 𝐶𝐹 = 0.7468
= 233 𝑔/𝑚𝑜𝑙
𝑤𝑡. 𝑜𝑓 𝑝𝑝𝑡 𝑥 𝐶𝐹
𝑀𝑊 𝑜𝑓 𝐻𝑔𝐶𝑙2 %= 𝑥 100
𝐶𝐹 = . 𝑤𝑡. 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
𝑀𝑊 𝑜𝑓 𝐻𝑔𝑆 0.9000 g 𝑥 0.7468
271 𝑔/𝑚𝑜𝑙 %= 𝑥 100
𝐶𝐹 = . 1.800 g
233 𝑔/𝑚𝑜𝑙 % = 𝟑𝟕. 𝟑𝟒% 𝒐𝒇 𝑲𝟐 𝑺𝑶𝟒
𝐶𝐹 = 1.1630

𝐴𝑙2 (𝑆𝑂4 )3 + 𝐵𝑎𝐶𝑙2 → 3𝐵𝑎𝑆𝑂4 ↓ +𝐴𝑙𝐶𝑙2

𝑤𝑡. 𝑜𝑓 𝑝𝑝𝑡 𝑥 𝐶𝐹
%= 𝑥 100
𝑤𝑡. 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒 𝐴𝑙2 (𝑆𝑂4 )3 = 23(2) + 32(3) + 16(4𝑥3)
0.1815 g 𝑥 1.1630 = 334 𝑔/𝑚𝑜𝑙
% 𝐻𝑔𝐶𝑙2 = 𝑥 100
0.2551 g
% 𝐻𝑔𝐶𝑙2 = 𝟖𝟐. 𝟕𝟓% 𝒐𝒇 𝑯𝒈𝑪𝒍𝟐 𝐵𝑎𝑆𝑂4 = 137(1) + 32(1) + 16 (4)
= 233 𝑔/𝑚𝑜𝑙
6) Calculate the equivalent amounts of each
and the percentage purity if the unknown in 𝑀𝑊 𝑜𝑓 𝐴𝑙2 (𝑆𝑂4 )3
𝐶𝐹 = .
prob. 4 were MgSO4, K2SO4, and 𝑀𝑊 𝑜𝑓 3𝐵𝑎𝑆𝑂4
Al2(SO4)3. 334 𝑔/𝑚𝑜𝑙
𝐶𝐹 = .
(3)233 𝑔/𝑚𝑜𝑙
𝑀𝑔𝑆𝑂4 + 𝐵𝑎𝐶𝑙2 → 𝐵𝑎𝑆𝑂4 ↓ +𝑀𝑔𝐶𝑙2 𝐶𝐹 = 0.4778
 𝑤𝑡. 𝑜𝑓 𝑝𝑝𝑡 𝑥 𝐶𝐹
%= 𝑥 100
𝑤𝑡. 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
0.9000 g 𝑥 0.4778
%= 𝑥 100
1.800 g
% = 𝟐𝟑. 𝟖𝟗% 𝒐𝒇 𝑨𝒍𝟐 (𝑺𝑶𝟒 )𝟑
 PHAN111LEC_WEEK 11
Extractives
• Product of extraction procedure
• Amount of extractives, which a drug yields
to a given solvent, is a measure of the
amount of certain constituents or group of
related constituents, which the drug
contains
• One solvent is not enough to extract all
constituents (like dissolves like)
Concepts
• Solvent used must not dissolve appreciable
quantities of substances other than those
sought in the extraction
• Amount of drug soluble is an index of its
purity for official requirements; low polarity
index = nonpolar and vice versa
• % extract (solvent-soluble residue)
• % insoluble residue – contains fibers and
cellulose, etc.
Properties of a Good Solvent
• Low toxicity
o Methanol is previously used as a
solvent but is now less used due to
its toxicity
• Ease of evaporation
• Rapid physiologic absorption of the extract
• Preservative action – ethanol is preferred as
a solvent than water
• Inert – inability to cause a complex
EXTRACTION METHODS
• Maceration – letting the substance sit in a
suitable solvent for a long period of time
• Percolation - filtration
• Digestion – gentle heat applied; for
thermolabile constituents
• Infusion – maceration through boiling or
simmering in water
• Decoction – boiling for 15 mins.
• Enfleurage – common in extraction of
volatile oils; wax as a solvent
• Continuous Extraction or Soxhlet
Extraction – exhaustive extraction
Extraction Procedures
• Soxhlet Apparatus – generally used for
extraction with volatile solvents wherein
small quantities of drug are extracted
o Thimble – area where the sample is
placed
𝑤𝑡. 𝑜𝑓 𝑟𝑒𝑠𝑖𝑑𝑢𝑒
% 𝑒𝑥𝑡𝑟𝑎𝑐𝑡𝑖𝑣𝑒 = 𝑥100
𝑤𝑡. 𝑜𝑓 𝑠𝑥.
𝑤𝑡. 𝑜𝑓 𝑠𝑥. 𝑖𝑛 𝑡ℎ𝑒 𝑡ℎ𝑖𝑚𝑏𝑙𝑒 𝑎𝑓𝑡𝑒𝑟 𝑑𝑟𝑦𝑖𝑛𝑔
% 𝑖𝑛𝑠𝑜𝑙. 𝑟𝑒𝑠𝑖𝑑𝑢𝑒 =
𝑤𝑡. 𝑜𝑓 𝑠𝑥.
𝑥100
Alcohol-Soluble Extractives
• For resins
𝐴𝑙𝑐. 𝑆𝑜𝑙. 𝐸𝑠𝑡𝑟𝑎𝑐𝑡 = 𝑤𝑡. 𝑜𝑓 𝑚𝑜𝑖𝑠𝑡𝑢𝑟𝑒 𝑓𝑟𝑒𝑒 𝑑𝑟𝑢𝑔 − 𝑤𝑡. 𝑜𝑓 𝑖𝑛𝑠𝑜𝑙. 𝑠𝑥.
Water-Soluble Extractives
• For drugs containing one or more important
constituents soluble in water
• Extraction is performed by maceration and
residue after drying to constant weight
𝑊𝑎𝑡𝑒𝑟 𝑆𝑜𝑙. 𝐸𝑠𝑡𝑟𝑎𝑐𝑡 = 𝑤𝑡. 𝑜𝑓 𝑟𝑒𝑠𝑖𝑑𝑢𝑒 𝑎𝑓𝑡𝑒𝑟 𝑑𝑟𝑦𝑖𝑛𝑔
Other Solvents
• Hexane – for fats and fixed oils through
continuous extraction
• Ether – for resins, fixed oils, coloring matter
and crude fiber through continuous
extraction
CRUDE FIBER CONTENT
• Residue consisting chiefly of cellulose that
remains undissolved after successive
treatment with boiling acid and alkali
• Important for food and animal feed Q.C. as it
determines the presence of adulterants
which are also the crude fiber or the plant
wastes
• Samples are exhausted with ether to
remove fats and waxes which prevents
penetration of the acid and alkali solution
into the drug particles
𝑤𝑡. 𝑜𝑓 𝑐𝑟𝑢𝑑𝑒 𝑓𝑖𝑏𝑒𝑟
%𝐶𝑟𝑢𝑑𝑒 𝐹𝑖𝑏𝑒𝑟 = 𝑥100
𝑤𝑡. 𝑜𝑓 𝑖𝑛𝑠𝑜𝑙 𝑟𝑒𝑠𝑖𝑑𝑢𝑒
𝑤𝑡. 𝑜𝑓 𝐶𝐹 = 𝑤𝑡. 𝑜𝑓 𝑎𝑠ℎ − 𝑤𝑡. 𝑜𝑓 𝑟𝑒𝑠𝑖𝑑𝑢𝑒
Determination of Crude Fiber Content
1. Solvent exhausted sample (found in the
thimble)
2. Add 200 mL of 1.25% boiling in H2SO4 for • Mercuric Potassium Iodide or Mayer’s
30 minutes Reagent – solution of 1.358 g of mercuric
3. Filter and wash the residue iodide in 60 mL of water with 5 g of KI in a
4. Rinse the residue back into the flask with 10 mL of water and the mixture diluted to
200 mL of boiling NaOH solution adjusted 100 mL. This reagent gives white or slightly
to exactly 1.25%. Again heat the mixture to yellow precipitate with dilute solution of
boiling and continue the boiling for exactly alkaloids
30 minutes
5. Filter through a linen or hardened filter
paper and wash the residue back into the
flask with 200 mL of boiling NaOH solution
adjusted to exactly 1.25%. Again, heat the
mixture to boiling for exactly 30 minutes
6. Under the reflux condenser, wash the
residue with boiling water until the last
washing is neutral, dry it at 110 degC until
of constant weight and note the weight
7. Incinerate the dried residue and weigh the
ash

EXTRACTION OF ALKALOIDS
• Alkaloids – chemical substances which are:
• Nonpolar solvents in solvent-solvent
o obtained from plant, animal or
extraction releases pressure
synthetic sources
o contains organic nitrogen within
Practice Problems
their chemical structure
1) A cocoa sample with a weight of 10.265 g
o usually possess physiological activity
was placed in a tared thimble and exacted
• Alkaloids (R3N) are sparingly soluble in
with either for 5 hours using continuous
water but readily soluble in most organic
extraction method. The ff. are the data
solvents immiscible in water ((ether,
collected.
chloroform (CHCL3), and carbon
tetrachloride (CCl4))
• Alkaloidal Salts (R3+NHCL-) are readily
soluble in water and sparingly soluble in
immiscible solvents
• Alkaloids form highly insoluble precipitates
with a considerable number of reagents with
the salts of some heavy metals such as
mercury, gold, and platinum

Alkaloidal Test Solutions 𝑤𝑡. 𝑜𝑓 𝐶𝐹 = 𝑤𝑡. 𝑜𝑓 𝑎𝑠ℎ − 𝑤𝑡. 𝑜𝑓 𝑟𝑒𝑠𝑖𝑑𝑢𝑒

• Mercuric Iodide TS or Valser’s Reagent – 𝑤𝑡. 𝑜𝑓 𝐶𝐹 = 2.1872 𝑔 − 1.9016 𝑔
prepared by slowly adding 10% solution of 𝑤𝑡. 𝑜𝑓 𝐶𝐹 = 0.2856 𝑔
potassium iodide to red mercuric iodide until
𝑤𝑡. 𝑜𝑓 𝑖𝑛𝑠𝑜𝑙. 𝑟𝑒𝑠𝑖𝑑𝑢𝑒 = 𝑤𝑡. 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒 𝑎𝑛𝑑 𝑡ℎ𝑖𝑚𝑏𝑙𝑒 𝑎𝑓𝑡𝑒𝑟 𝑒𝑥𝑡𝑟𝑎𝑐𝑡𝑖𝑜𝑛
almost all the red mercuric iodide is − 𝑤𝑡. 𝑜𝑓 𝑡𝑎𝑟𝑒𝑑 𝑡ℎ𝑖𝑚𝑏𝑙𝑒
dissolved. The excess mercuric iodide is then 𝑤𝑡. 𝑜𝑓 𝑖𝑛𝑠𝑜𝑙. 𝑟𝑒𝑠𝑖𝑑𝑢𝑒 = 5.0092 𝑔 − 0.9285 𝑔
removed by filtration. This reagent forms a 𝑤𝑡. 𝑜𝑓 𝑖𝑛𝑠𝑜𝑙. 𝑟𝑒𝑠𝑖𝑑𝑢𝑒 = 4.0807 𝑔
white precipitate
• Iodine TS or Wagner’s Reagent – contains
iodine and potassium iodide dissolved in 𝑤𝑡. 𝑜𝑓 𝑐𝑟𝑢𝑑𝑒 𝑓𝑖𝑏𝑒𝑟
%𝐶𝑟𝑢𝑑𝑒 𝐹𝑖𝑏𝑒𝑟 = 𝑥100
distilled water. A 0.1 N Iodine solution may 𝑤𝑡. 𝑜𝑓 𝑖𝑛𝑠𝑜𝑙 𝑟𝑒𝑠𝑖𝑑𝑢𝑒
be employed; this yields a reddish or red- 0.2856 𝑔
%𝐶𝑟𝑢𝑑𝑒 𝐹𝑖𝑏𝑒𝑟 = 𝑥100
brown precipitate 4.0807 𝑔
%𝐶𝑟𝑢𝑑𝑒 𝐹𝑖𝑏𝑒𝑟 = 𝟔. 𝟗𝟗𝟗𝟖%; 𝒚𝒆𝒔 𝒊𝒕 𝒄𝒐𝒏𝒇𝒐𝒓𝒎𝒔
 [(20 mL x 0.1200 N ) − (12.10 mL x 0.1100 N)](0.2102 𝑔/𝑚𝐸𝑞)
%𝑅3 𝑁 = 𝑥100
0.3120 g
𝑤𝑡. 𝑜𝑓 𝑟𝑒𝑠𝑖𝑑𝑢𝑒
% 𝑒𝑥𝑡𝑟𝑎𝑐𝑡𝑖𝑣𝑒 = 𝑥100 %𝑅3 𝑁 = 𝟕𝟐. 𝟎𝟐% 𝒘/𝒘 𝒐𝒇 𝒂𝒎𝒊𝒏𝒐𝒑𝒉𝒚𝒍𝒍𝒊𝒏𝒆
𝑤𝑡. 𝑜𝑓 𝑠𝑥.
41.9875 𝑔 − 38.9966 𝑔
% 𝑒𝑥𝑡𝑟𝑎𝑐𝑡𝑖𝑣𝑒 = 𝑥100
10.265 g 4) 20 tablets of codeine sulfate (3/4 grain) is
% 𝑒𝑥𝑡𝑟𝑎𝑐𝑡𝑖𝑣𝑒 = 𝟐𝟗. 𝟏𝟒%; 𝒏𝒐 𝒊𝒕 𝒅𝒐𝒆𝒔 𝒏𝒐𝒕 𝒄𝒐𝒏𝒇𝒐𝒓𝒎 weighing 1.66 gram. An aliquot portion
weighing 0.5589 g was extracted with
2) Determine % w/w of alkaloids in belladonna chloroform and the extract was evaporated
leaf if 15.00 mL of 0.0210 N H2SO4 was and dried at 100 degC for 2 hours leaving a
added to the extracted alkaloids, and 7.30 residue which weighed 0.305 g. Compute
mL of 0.0198 N NaOH for the residual for the percentage labeled amount.
titration. The weight of the powder of a. Average wt. of tab = 1.66 g/20
belladonna leaf was 1.021 g. Each mL of tablets
0.02 N sulfuric acid is equivalent to 5.788 b. Labeled amount = ¾ grain = 1 gr. =
mg of hyoscyamine 65 mg
c. % purity/assay = wt. of residue/wt.
𝑡𝑖𝑡𝑒𝑟 = 𝑁(𝑚𝐸𝑞) of sample x 100
𝑡𝑖𝑡𝑒𝑟 𝑁(𝑚𝐸𝑞)
=
𝑁 𝑁 𝑤𝑡. 𝑝𝑒𝑟 𝑡𝑎𝑏 = 1.66 𝑔/20 𝑡𝑎𝑏𝑙𝑒𝑡𝑠
𝑡𝑖𝑡𝑒𝑟
= 𝑚𝐸𝑞 = 0.083 𝑔/𝑡𝑎𝑏 𝑜𝑟 83 𝑚𝑔/𝑡𝑎𝑏
𝑁
3 65 𝑚𝑔
5.788 mg 𝑔𝑟𝑎𝑖𝑛 𝑥 = 48.75 𝑚𝑔
= 𝑚𝐸𝑞 4 1 𝑔𝑟
0.02 N
289.4 𝑚𝑔/𝑚𝐸𝑞 𝑜𝑟 0.2894 𝑔/𝑚𝐸𝑞 = 𝑚𝐸𝑞
𝑤𝑡. 𝑜𝑓 𝑟𝑒𝑠𝑖𝑑𝑢𝑒
%𝑎𝑠𝑠𝑎𝑦 = 𝑥100
𝑤𝑡. 𝑜𝑓 𝑠𝑥
[(𝑉1 𝑁2 ) − (𝑉2 𝑁2 )](𝑚𝐸𝑞) 0.305 g
%𝑅3 𝑁 = 𝑥100 %𝑎𝑠𝑠𝑎𝑦 = 𝑥100
𝑤𝑡. 0.5589 g
%𝑅3 𝑁 =
[(15.00 mL x 0.0210 N ) − (7.30 mL x 0.0198 N )](0.2894 𝑔/𝑚𝐸𝑞)
𝑥100 %𝑎𝑠𝑠𝑎𝑦 = 54.57%
1.021 g
%𝑅3 𝑁 = 𝟒. 𝟖𝟑% 𝒘/𝒘 𝒂𝒍𝒌𝒂𝒍𝒐𝒊𝒅𝒔
𝑤𝑡. 𝑜𝑓 𝑟𝑒𝑠𝑖𝑑𝑢𝑒
3) Calculate the % w/w aminophylline if 𝑙𝑎𝑏𝑒𝑙𝑒𝑑 𝑎𝑚𝑜𝑢𝑛𝑡 = 𝑥 𝑎𝑣𝑒. 𝑤𝑡.
𝑤𝑡. 𝑜𝑓 𝑠𝑥
0.3120 g sample, assayed following the
0.305 𝑔
procedure given, required 12.10 mL of 𝑙𝑎𝑏𝑒𝑙𝑒𝑑 𝑎𝑚𝑜𝑢𝑛𝑡(𝑚𝑔) = 𝑥 83 𝑚𝑔/𝑡𝑎𝑏
0.1100N NH4SCN to bring about the 0.5589 𝑔
endpoint in the residual titration of silver 𝑙𝑎𝑏𝑒𝑙𝑒𝑑 𝑎𝑚𝑜𝑢𝑛𝑡(𝑚𝑔) = 45.29 𝑚𝑔/𝑡𝑎𝑏
nitrate. Exactly 20 mL of 0.1200 N AgNO3
𝑎𝑐𝑡𝑢𝑎𝑙 𝑤𝑡.
was taken initially. The titer value for 1 mL %𝑙𝑎𝑏𝑒𝑙𝑒𝑑 𝑎𝑚𝑜𝑢𝑛𝑡 = 𝑥100
of 0.1 N AgNO3 is 21.02 mg aminophylline 𝑡ℎ𝑒𝑜𝑟𝑒𝑡𝑖𝑐𝑎𝑙 𝑤𝑡.
45.29 𝑚𝑔/𝑡𝑎𝑏
%𝑙𝑎𝑏𝑒𝑙𝑒𝑑 𝑎𝑚𝑜𝑢𝑛𝑡 = 𝑥100
𝑡𝑖𝑡𝑒𝑟 = 𝑁(𝑚𝐸𝑞) 48.75 𝑚𝑔
𝑡𝑖𝑡𝑒𝑟 𝑁(𝑚𝐸𝑞) %𝑙𝑎𝑏𝑒𝑙𝑒𝑑 𝑎𝑚𝑜𝑢𝑛𝑡
= = 𝟗𝟐. 𝟗𝟎% 𝒐𝒇 𝒄𝒐𝒅𝒆𝒊𝒏𝒆 𝒔𝒖𝒍𝒇𝒂𝒕𝒆/𝒕𝒂𝒃
𝑁 𝑁
𝑡𝑖𝑡𝑒𝑟
= 𝑚𝐸𝑞
𝑁
5) The weight of 20 tablets of morphine sulfate
21.02 mg (150 mg) is 3.075 g. If 0.3075 g was used in
= 𝑚𝐸𝑞 the assay and it required 10.3 mL of 0.023 N
0.1 N
210.2 𝑚𝑔/𝑚𝐸𝑞 𝑜𝑟 0.2102 𝑔/𝑚𝐸𝑞 = 𝑚𝐸𝑞 NaOH to back titrate, 25 mL of 0.021 N
H2SO4. Calculate the percent labeled
amount of morphine sulfate. Each mL of 1 N
[(𝑉1 𝑁2 ) − (𝑉2 𝑁2 )](𝑚𝐸𝑞) H2SO4 is equivalent to 758.83 mg of
%𝑅3 𝑁 = 𝑥100
𝑤𝑡. morphine sulfate.
 𝑤𝑡. 𝑝𝑒𝑟 𝑡𝑎𝑏 = 3.075 g/20 𝑡𝑎𝑏𝑙𝑒𝑡𝑠
= 0.15375 𝑔/𝑡𝑎𝑏 𝑜𝑟 153.75 𝑚𝑔/𝑡𝑎𝑏

𝑡𝑖𝑡𝑒𝑟 = 𝑁(𝑚𝐸𝑞)
𝑡𝑖𝑡𝑒𝑟 𝑁(𝑚𝐸𝑞)
=
𝑁 𝑁
𝑡𝑖𝑡𝑒𝑟
= 𝑚𝐸𝑞
𝑁

758.83
= 𝑚𝐸𝑞
1N
758.83 𝑚𝑔/𝑚𝐸𝑞 𝑜𝑟 0.75883 𝑔/𝑚𝐸𝑞 = 𝑚𝐸𝑞

[(𝑉1 𝑁2 ) − (𝑉2 𝑁2 )](𝑚𝐸𝑞)

𝑚𝑔/𝑡𝑎𝑏 = 𝑥100
𝑤𝑡.
(10.3
[(25 mL x 0.021 N) − mL x 0.023 N)](0.75883 𝑔/𝑚𝐸𝑞)
𝑚𝑔/𝑡𝑎𝑏 = 𝑥 153.75 𝑚𝑔/𝑡𝑎𝑏
0.3075 g
%𝑎𝑠𝑠𝑎𝑦 = 109.31 𝑚𝑔/𝑡𝑎𝑏

𝑎𝑐𝑡𝑢𝑎𝑙 𝑤𝑡.
%𝑙𝑎𝑏𝑒𝑙𝑒𝑑 𝑎𝑚𝑜𝑢𝑛𝑡 = 𝑥100
𝑡ℎ𝑒𝑜𝑟𝑒𝑡𝑖𝑐𝑎𝑙 𝑤𝑡.
109.31 𝑚𝑔
%𝑙𝑎𝑏𝑒𝑙𝑒𝑑 𝑎𝑚𝑜𝑢𝑛𝑡 = 𝑥100
150 mg
%𝑙𝑎𝑏𝑒𝑙𝑒𝑑 𝑎𝑚𝑜𝑢𝑛𝑡 = 𝟕𝟐. 𝟖𝟕%
 PHAN111LEC_WEEK 12
Water Content
• Moisture Determination – necessary to
specify certain water content limits in drug
monographs and ensure uniformity in official
pharmaceuticals; water can be:
o Water of crystallization (hydrates)
o Water in the Absorbed form
• When crude drugs are sold with guaranteed
assay of active constituent, percent of API
must be calculated on the basis of a
moisture-free drug due to its influence in the
calculated results
Water Content Determination Methods
A. Gravimetric Method – for drugs containing
no constituents other than water, volatile at
105 degC; it takes 5 hours to determine the
moisture content; sample needed must be
10 grams; Drying Constant Weight – after 5
hours, cool the sample in a dessicator, and
then weigh; two consecutive weighs with no
more than 0.5 milligrams difference; no
moisture left
B. Gravimetric Method – for drugs containing
ether-soluble constituents, volatile at 105
degC
C. Azeotropic Method/Toluene Distillation –
for vegetable drugs containing 2% or more
moisture; azeotrope (mixture of two liquids
which each component doesn’t change)
a. Toluene-solvent in NF
b. Xylene-solvent in USP
D. Titrimetric Method/Karl Fischer Method –
for crystalline compounds that contains
water of hydration or absorbed water
E. Dew Point Method – for determining water
at very low concentration
F. Electrolytic Hygrometric – for determining
extremely low concentration of water
Azeotropic Method / Toluene Distillation
• When the water has distilled over, rinse the
condenser tube with toluene. Continue the
distillation for 5 minutes, remove the heat,
and allow the receiving tube to cool to room
temp. When the water and toluene have
separated completely, read the volume of
water and calculate the percent of moisture
in the sample
% 𝑚𝑜𝑖𝑠𝑡𝑢𝑟𝑒 =
𝑣𝑜𝑙𝑢𝑚𝑒 𝑜𝑓 𝑤𝑎𝑡𝑒𝑟
𝑥100
𝑤𝑡. 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
Titrimetric Method / Karl Fischer Method
• Coulometric Method
• Most chemical compounds are relatively
stable at room temperature
• Substances that release water can affect
results
• For crystalline compounds that contains
water in their molecular weight
• Most rapid that requires only a small sample
and is specific for water
• Involves titration of sample in reagent
methanol with Karl Fischer Reagent
containing:
o Sulfur Dioxide – reacts with water;
added second
o Iodine – reacts with water; added
second; forms sulfurtrioxide
o Pyridine – prevents reverse reaction;
added last
o Methanol (anhydrous) – prevents the
pyridine-sulfur complex; added first
to form hydroiodic acid
• Karl Fischer Reagent – concentration such
that 1 mL of the reagent is equivalent to
approximately 5 mg of water; deteriorates
gradually; standardized with sodium tartrate
(𝑁𝑎2 𝐶4 𝐻4 𝑂6 • 2𝐻2 𝑂); endpoint is canary
yellow
0.1566 𝑥 𝑚𝑔 𝑜𝑓 𝑠𝑜𝑑𝑖𝑢𝑚 𝑡𝑎𝑟𝑡𝑟𝑎𝑡𝑒
𝐹=
𝑚𝐿 𝑜𝑓 𝑟𝑒𝑎𝑔𝑒𝑛𝑡 𝑟𝑒𝑞𝑢𝑖𝑟𝑒𝑑
𝑤ℎ𝑒𝑟𝑒 𝐹 𝑟𝑒𝑓𝑒𝑟𝑠 𝑡𝑜 𝒘𝒂𝒕𝒆𝒓 𝒐𝒇 𝒆𝒒𝒖𝒊𝒗𝒂𝒍𝒆𝒏𝒄𝒆
2𝐻2 𝑂 36.04
𝑤𝑡. 𝑜𝑓 𝑤𝑎𝑡𝑒𝑟 = =
𝑁𝑎2 𝐶4 𝐻4 𝑂6 • 2𝐻2 𝑂 230.88
= 0.1566
• Formula:
𝑤𝑎𝑡𝑒 𝑐𝑜𝑛𝑡𝑒𝑛𝑡 = 𝑆 𝑜𝑟 𝑣𝑜𝑙. 𝑜𝑓 𝑟𝑒𝑎𝑔𝑒𝑛𝑡 𝑥 𝐹
𝑆𝑥𝐹
% 𝐻2 𝑂 = 𝑥100
𝑚𝑔. 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
• Karl Fischer Titrators
 8.5 mL to reach the canary yellow endpoint,
determine the water content of citric acid.

0.1566 𝑥 𝑚𝑔 𝑜𝑓 𝑠𝑜𝑑𝑖𝑢𝑚 𝑡𝑎𝑟𝑡𝑟𝑎𝑡𝑒

𝐹=
𝑚𝐿 𝑜𝑓 𝑟𝑒𝑎𝑔𝑒𝑛𝑡 𝑟𝑒𝑞𝑢𝑖𝑟𝑒𝑑
0.1566 𝑥 350 𝑚𝑔
𝐹=
8.5 𝑚𝐿
𝐹 = 6.4482 𝑚𝑔/𝑚𝐿

Dew Point Method

𝑆𝑥𝐹
• The amount of water vapor in a system may % 𝐻2 𝑂 = 𝑥100
be determined by noting the temperature at 𝑚𝑔. 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
which a dew or a mist forms when the 20 𝑚𝐿 𝑥 6.4482 𝑚𝑔/𝑚𝐿
% 𝐻2 𝑂 = 𝑥100
system is suddenly cooled under adiabatic 4800 𝑚𝑔
expansion following release of compression % 𝐻2 𝑂 = 2.69% 𝑜𝑓 𝑤𝑎𝑡𝑒𝑟 𝑐𝑜𝑛𝑡𝑒𝑛𝑡 𝑖𝑛 𝐶𝑖𝑡𝑟𝑖𝑐 𝐴𝑐𝑖𝑑
Electrolytic Hygrometric Method
• Principle: Selective Electrolysis of water 2) Calculate the water content of an antibiotic
• Amount of electric current is a measure of powder using 350 mg sample. The water
water content equivalence factor (F) of the Karl Fischer
reagent is 4.6, and the volume of the
Ash Content Determination reagent used was 9.2 mL. The % of water
• Total Ash – representation of organic content is…
substances; if mataaas yung ash content,
𝑆𝑥𝐹
hindi maganda; may limits ang ash content % 𝐻2 𝑂 = 𝑥100
• Acid Insoluble Ash – part of total ash that is 𝑚𝑔. 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
insoluble in 2N HCl % 𝐻2 𝑂 = 12.09% 𝑜𝑓 𝑤𝑎𝑡𝑒𝑟 𝑐𝑜𝑛𝑡𝑒𝑛𝑡
• Water soluble Ash
• Sulfates Ash 3) From the following data, compute for the %
content and % acid insoluble ash.
a. Wt. of empty crucible = 26.630 g
b. Wt. of crucible drug = 2.030 g
c. Wt. of crucible with ash = 26.970 g
d. Wt. of crucible and acid insoluble ash
= 26.710 g

𝑇𝑜𝑡𝑎𝑙 𝐴𝑠ℎ (%)

𝑤𝑡. 𝑜𝑓 𝑡𝑜𝑡𝑎𝑙 𝑎𝑠ℎ/𝑎𝑐𝑖𝑑 𝑖𝑛𝑠𝑜𝑙𝑢𝑏𝑙𝑒 𝑎𝑠ℎ
= 𝑥 100
𝑤𝑡. 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒 𝑢𝑠𝑒𝑑

Practice
1) Moisture content of citric acid was
determined by the Karl-Fischer Method, and
the following data were obtained. Wt. of
Citric Acid = 4.8 g, Vol. of reagent consumed
= 20 mL. The water equivalence factor of
the reagent was determined by titrating
0.350 g of sodium tartrate, and consumed
 PHAN111LEC_WEEK 13
Analysis of Fats and Fixed Oils and Fatty
Substances
• Constant – value or number of physical and
chemical property
o Specific gravity
o Melting point
o Congealing point
o Refractive index
o Optical activity
o Acid value, saponification value,
ester value, iodine value, acetyl
value, hydroxyl value, unsaponifiable
matter, water, and sediment
• Purity of fixed oils, fats, waxes, and resins,
etc. can’t be ascertained by the usual
methods based on gravimetric and
volumetric processes
Concepts
• Fats – compounds consisting of fatty acids
combined with glycerol via ester linkages
• Fixed Oils – mixture of relatively high
quantities of liquid glycerides (glyceryl
oleate)
• Fats – contains large amounts of solid
glycerides (glyceryl stearate)
o Butyric – 4C
o Caproic – 6C
o Caprylic – 8C
o Capric – 10C
o Palmitic – 16C
o Stearic – saturated; 18C
o Oleic – unsaturated; 18C
• Waxes – esters of high MW monohydric
alcohols and high MW fatty acids
• Balsams – contains benzoic or amino acids
or their esters
• Resins – natural or induced solid or semi-
solid exudates from plants characterized by
being insoluble in water, soluble in alcohol
and ether, crystallizable and softening or
melting at a moderate heat
Preparation of the Sample of Fats and Oils
• For determination, samples should undergo
preliminary treatment if they are turbid due
to separation of stearin
• Such oils should be made clear by heating
their container on a water bath at 50 degC
until the turbidity disappears
• If warming the oil fails to clarify, it should be
filtered through a dry filter paper in a funnel
held in a hot water jacket
Analysis of Fats and Oils
• Determine the specific gravity and melting
point of the sample
• Acid Value/Acid Number/Acidity Index
o Liberation of free acids due to ester
hydrolysis from the catalytic action
of light and heat, by bacterial action,
or by chemical treatment
o High Acid Value DOES NOT indicate
rancidity but hydrolytic
decomposition during their
preparation, purification, or storage
o Number of milligrams of potassium
hydroxide required to neutralize the
free acids in 1 g of sample
o Expressed as the number of
milliliters of 0.1 N NaOH required to
neutralize the free acids in 10 grams
of sample
Acid Value Determination
• Unless otherwise directed, dissolve about
10.0 g of the substance, accurately weighed,
in 50 mL of a mixture of equal volumes of
alcohol and ether in a flask
• If the test specimen does not dissolve in the
cold solvent, connect the flask with a
suitable condenser and warm slowly, with
frequent shaking, until the specimen
dissolves
• Add 1 mL of HPH TS, and titrate with 0.1N
KOH VS or 0.1N NaOH VS until solution
remains faintly pink after shaking for 30
seconds
(56.11 𝑚𝑔/𝑚𝐸𝑞)(𝑚𝐿)(𝑁)
𝐴𝑉 =
𝑤𝑡. 𝑜𝑓 𝑠𝑥
𝑚𝐿 𝑜𝑓 0.1𝑁 𝑁𝑎𝑂𝐻
𝐴𝑉 = 𝑥2
𝑤𝑡. 𝑜𝑓 𝑠𝑥
 Wherein 2 is based on the amount indicated in
specification
Saponification Value
• A.k.a. Koettsdorfer Number or
Saponification Number
• Defined as the number of KOH in mg
required to neutralize the free fatty acids
and saponify the esters in 1 g of sample
• Helps detect the presence of glycerides
which contain less than 16 or more than 18
carbon atoms due to the fact that SV is
inversely proportional to the average of the
MW of fatty acids found in the sample
• High SV = low MW fatty acids
Ex.
Saponification Value of Cottonseed Oil
o Place 1.5-2 g of sample accurately
weighed in a 250 mL flask
o Add to it exactly 25 mL of alcoholic
0.5N KOH (alcohol acts as solvent
for the oil and saponification
products which are insol. in water).
Reflux on a water bath for 30
minutes frequently rotating the
contents until saponification is
complete
o Add 1 mL of HPH and titrate the
excess KOH with 0.5N HCl. (HCL
cannot be substituted with H2SO4
which will yield K2SO4 that will not
dissolve in alcoholic solution)
o Perform a blank test (performed to
eliminate errors from all sources)
% 𝑈𝑛𝑠𝑎𝑝𝑜𝑛𝑖𝑓𝑖𝑎𝑏𝑙𝑒 𝑀𝑎𝑡𝑡𝑒𝑟 =
𝑆𝑉
(𝑚𝐿 𝑜𝑓 𝐻𝐶𝑙𝑏𝑙𝑎𝑛𝑘 − 𝑚𝐿 𝑜𝑓 𝐻𝐶𝑙𝑠𝑎𝑚𝑝𝑙𝑒 )(𝑁)(56.11 𝑚𝑔/𝑚𝐸𝑞)
=
𝑤𝑡. 𝑜𝑓 𝑠𝑥.
Ex.
Ester Value
• A.k.a. Ester Number
• Defined as number of KOH in mg required
to saponify esters in 1 g of substance
• Substances that do not contain free acids
have equal EV and SV
• Substances that have fatty acids have EV =
AV – SV
• Important in the analysis of beeswax, which
indicates the presence of adulterants like
paraffin which consists of high MW that
would abnormally increase AV and lowers
EV
𝑚𝐿 (𝑁)(𝑚𝐸𝑞)
𝐸𝑉 = 𝑥 1000
𝑤𝑡. 𝑜𝑓 𝑠𝑥.
𝐸𝑉 = 𝑆𝑉 (𝑤/𝑜 𝑓𝑎𝑡𝑡𝑦 𝑎𝑐𝑖𝑑𝑠)
𝐸𝑉 = 𝐴𝑉 − 𝑆𝑉 (𝑤/ 𝑓𝑎𝑡𝑡𝑦 𝑎𝑐𝑖𝑑𝑠)
Unsaponifiable Matter
• Substances that are not saponified by alkali
hydroxides but are soluble in ordinary fat
solvents
• After saponification, a small amount of
residue is left consisting of phytosterol if the
oils or fats are of vegetable origin and
cholesterol if they are of animal origin
• Determination of this constant will indicate
the presence of unsaponifiable adulterants
such as petroleum oil added to linseed oil
𝑤𝑡. 𝑜𝑓 𝑟𝑒𝑠𝑖𝑑𝑢𝑒
𝑥100
𝑤𝑡. 𝑜𝑓 𝑠𝑥.
 Determination of Unsaponifiable Matter
o Transfer about 5.0 g of the oil or fat,
accurately weighed, to a 250 mL
conical flask, add 50 mL of an
alcoholic KOH and heat the flask on
a steam bath under a suitable
condenser to maintain reflux for 1
hour, swirling frequently
o Cool to a temperature below 25, and
transfer the contents of the flask to a
separator having a
polytetrafluoroethylene stopcock,
rinsing the flask with two 50 mL
portions of water that are added to
the separator
o Extract with three 100 mL portions
of ether, combining with the ether
extracts in another separator
containing 40 mL of water
o Allow the mixture to separate, and
discard the lower aqueous phase.
Wash the ether extract with two
additional 40 mL portions of water,
and discard the lower aqueous
phase. Wash the ether extract
successively with a 40 mL portion of
KOH solution (3 in 100) and a 40 mL
portion of water
o Wash the ether extract with 40 mL
portions of water until the last
washing is not reddened by the
addition of 2 drops of HPH TS.
Transfer the ether extract to a tared
flask, and rinse the separator with 10
mL of ether, adding the rinsing to the
flask.
o Evaporate the ether on a steam bath,
and add 6 mL of acetone to the
residue. Remove the acetone in a
current of air, and dry the residue at
105 degC until successive weighing
differ by not more than 1 mg
Iodine Value
• A.k.a. Iodine Number
• Defined as the number of grams of iodine
absorbed under specified condition by 100
grams of substance
• Quantitative measure of the proportion of
unsaturated fatty acids presents in both free
and combined esters that have the property
of absorbing iodine
• Indicate a pure or a mixture
• Type of Fixed Oils Based on Iodine Value:
o Drying >120 - LiCod
o Semi-Drying 100-120 - CotSe
o Non-Drying <100 – OlAf
• Methods of Determination for IV
o Method I or Hanus Method – uses
iodobromide in 𝐶𝐻𝐶𝑙3
o Method II or Wijs Method – uses
iodochloride in 𝐶𝐶𝑙4
(𝑚𝐿 𝑜𝑓 𝑏𝑙𝑎𝑛𝑘 − 𝑚𝐿 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒)(𝑁)(𝑚𝐸𝑞)
𝑔 𝐼2 = 𝑥100
𝑤𝑡. 𝑜𝑓 𝑠𝑥.
Ex.
Iodine Value Determination
o Introduce 200 mg of olive oil
accurately weighed into a 250 mL
iodine flask
o Add 20 mL of carbon tetrachloride
and after the oil has dissolve add 25
mL of iodochloride TS accurately
measured from a burette
o Stopper the vessel, shake and allow
it to stand for 30 minutes protected
from light
o Then add 20 mL of potassium iodide
TS and 100 mL of recently boiled
and cooled water
o Titrate the liberated iodine with 0.1N
Sodium Thiosulfate. When the iodine
color becomes quite pale, add 1 mL
of Starch TS and continue the
titration until the blue color is
discharged
o Perform a blank test
Hydroxyl Value
• A.k.a. Hydroxyl Number
• Defined as number of mg of KOH
equivalent to the hydroxyl content of 1 g of
substance
• Gives indication of the identity and purity of
fatty substances possessing alcoholic
hydroxyl groups
• Low HV = adulteration with high MW
alcohols or with non-alcoholic fatty
substances (i.e. paraffine, and petroleum oil)
Acetyl Value of Fatty Acids
• Expressed as number of mg of KOH
required to neutralize the acetic acid
obtained by saponification of 1 g of
acetylated fatty acids
• Corresponds closely to the hydroxyl value of
fatty alcohol and the two constants have
much the same significance with respect to
identity and purity of substances
• Determined by acetylating hydroxy fatty
acids
• From the saponification value of acetylated
fatty acid and avid value of the original fatty
acid, acetyl value is determined
Other Constants
• Peroxide Value – no., in mEq of oxygen, of
peroxides in 1 g of sample
• Anisidine Value – defined as 100 times the
absorbance (at 350 mm) of a solution
resulting form reaction of 1 g of fat in 100
mL of solvent
• Total Oxidation Value – combined PV and
Anisidine Value (2PV + AV)
• Solidification Temperature of FA –
congealing point
• Fatty Acid Composition
Practice
1) Find the acid number of a rosin sample
weighing 1.100 g which required 28 mL of
0.1100 N to bring the endpoint
(56.11 𝑚𝑔/𝑚𝐸𝑞)(𝑚𝐿)(𝑁)
𝐴𝑉 =
𝑤𝑡. 𝑜𝑓 𝑠𝑥
(56.11 𝑚𝑔/𝑚𝐸𝑞)(28 mL)(0.1100 N)
𝐴𝑉 =
1.100 g
𝐴𝑉 = 𝟏𝟓𝟕. 𝟏𝟏 𝒎𝒈/𝒈
2) If 2 g sample of cod liver oil required 4.5 mL
of 0.02N NaOH in the titration of fatty
acids, would it conform with the
specification? AV is not more than 1 mL of
0.1N NaOH in 2 grams of sample is required.
(56.11 𝑚𝑔/𝑚𝐸𝑞)(𝑚𝐿)(𝑁)
𝐴𝑉 =
𝑤𝑡. 𝑜𝑓 𝑠𝑥
(56.11 𝑚𝑔/𝑚𝐸𝑞)(4.5 mL)(0.02)
𝐴𝑉 =
2g
𝐴𝑉 = 𝟐. 𝟓𝟐 𝒎𝒈/𝒈; 𝒚𝒆𝒔, 𝒊𝒕 𝒄𝒐𝒏𝒇𝒐𝒓𝒎𝒔
𝑁1 𝑉1 = 𝑁2 𝑉2
(0.02N )(4.5 mL) (0.1𝑁)𝑉2
= evaporated to dryness on a water bath. The
0.1𝑁 0.1𝑁
0.9 𝑚𝐿 = 𝑉2
0.9 𝑚𝐿
𝐴𝑉 = 𝑥2
2g
𝐴𝑉 = 𝟎. 𝟗 𝒎𝑳
3) Find the SV of cottonseed oil if a 1.532 g
sample was refluxed with 25 mL of about
0.5N alcoholic KOH, required 15.70 mL of
0.5100N HCl for the residual titration. The
blank was run using the same volume of
0.5N of alcoholic KOH and required 26 mL
of 0.5100N of HCl to bring about the
endpoint. Does it fit the USP specs of 190-
198?
(𝑚𝐿 𝑜𝑓 𝐻𝐶𝑙𝑏𝑙𝑎𝑛𝑘 − 𝑚𝐿 𝑜𝑓 𝐻𝐶𝑙𝑠𝑎𝑚𝑝𝑙𝑒 )(𝑁)(56.11)
𝑆𝑉 =
𝑤𝑡. 𝑜𝑓 𝑠𝑥.
(26 mL − 15.70 mL)(0.5100N )(56.11)
𝑆𝑉 =
1.532 g
𝑆𝑉 = 𝟏𝟗𝟐. 𝟑𝟗; 𝒚𝒆𝒔, 𝒊𝒕 𝒄𝒐𝒏𝒇𝒐𝒓𝒎𝒔
4) A corn oil sample weighs 1.60 g was
saponified with 25 mL of alcoholic KOH and
required 9.0 mL of 0.5N HCl to titrate the
excess KOH. In the blank determination, 20
mL of 0.5N HCl was required to titrate the
alkali. Calculate the SV? USP specs should
be 187-193
(𝑚𝐿 𝑜𝑓 𝐻𝐶𝑙𝑏𝑙𝑎𝑛𝑘 − 𝑚𝐿 𝑜𝑓 𝐻𝐶𝑙𝑠𝑎𝑚𝑝𝑙𝑒 )(𝑁)(56.11)
𝑆𝑉 =
𝑤𝑡. 𝑜𝑓 𝑠𝑥.
(20 mL − 9.0 mL )(0.5N )(56.11)
𝑆𝑉 =
1.60 g
𝑆𝑉 = 𝟏𝟗𝟐. 𝟖𝟖; 𝒄𝒐𝒏𝒇𝒐𝒓𝒎𝒔
5) Beeswax sample has an acid value of 20.4
and saponification value of 89.8. Determine
the ester value of the sample. USP specs
should be between 72-77
𝐸𝑉 = 𝐴𝑉 − 𝑆𝑉
𝐸𝑉 = 20.4 − 89.8
𝐸𝑉 = 𝟔𝟗. 𝟒; 𝐝𝐨𝐞𝐬 𝐧𝐨𝐭 𝐜𝐨𝐧𝐟𝐨𝐫𝐦
6) A 4.09 g sample was treated with KOH
dissolved in alcohol and heated under a
reflux condenser. The ether extract was
residue left is 0.053 g. Calculate the %
Unsaponifiable Matter
𝑤𝑡. 𝑜𝑓 𝑟𝑒𝑠𝑖𝑑𝑢𝑒
% 𝑈𝑛𝑠𝑎𝑝𝑜𝑛𝑖𝑓𝑖𝑎𝑏𝑙𝑒 𝑀𝑎𝑡𝑡𝑒𝑟 = 𝑥100
𝑤𝑡. 𝑜𝑓 𝑠𝑥.
 0.053 g
% 𝑈𝑛𝑠𝑎𝑝𝑜𝑛𝑖𝑓𝑖𝑎𝑏𝑙𝑒 𝑀𝑎𝑡𝑡𝑒𝑟 = 𝑥100
4.09 g
% 𝑈𝑛𝑠𝑎𝑝𝑜𝑛𝑖𝑓𝑖𝑎𝑏𝑙𝑒 𝑀𝑎𝑡𝑡𝑒𝑟 = 𝟏. 𝟑𝟎%
7) A 0.1194 g sample was dissolved in 𝐶𝐻𝐶𝑙3 .
Twenty-five mL of ICl was added, stoppered,
and allowed to stand for 30 mins. KI was
added and titrated with 8.9 mL of 0.1024 N
Sodium thiosulfate. The blank test
consumed 24 mL of the titrant.
𝐼2 = 127 𝑔/𝑚𝑜𝐿
= 127/1(1000)
𝐼2 = 0.127 𝑔/𝑚𝐸𝑞
(𝑚𝐿 𝑜𝑓 𝑏𝑙𝑎𝑛𝑘 − 𝑚𝐿 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒)(𝑁)(𝑚𝐸𝑞)
𝑔 𝐼2 = 𝑥100
𝑤𝑡. 𝑜𝑓 𝑠𝑥.
(24 mL − 8.9 mL)(0.1024 N)(0.127 𝑔/𝑚𝐸𝑞)
𝑔 𝐼2 =
0.1194 g
𝑔 𝐼2 = 𝟏𝟔𝟒. 𝟒𝟕%
8) Determine the iodine value of a sample of
olive oil weighing 0.2100 g if 24.15 mL and
12 mL of 0.1100N sodium thiosulfate are
required for the blank and residual titrations.
Does it conform to USP specs of 79-88?
𝐼2 = 127 𝑔/𝑚𝑜𝐿
= 127/1(1000)
𝐼2 = 0.127 𝑔/𝑚𝐸𝑞
(𝑚𝐿 𝑜𝑓 𝑏𝑙𝑎𝑛𝑘 − 𝑚𝐿 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒)(𝑁)(𝑚𝐸𝑞)
𝑔 𝐼2 = 𝑥100
𝑤𝑡. 𝑜𝑓 𝑠𝑥.
(24.15 − 12 mL )(0.1100N)(0.127 𝑔/𝑚𝐸𝑞 )
𝑔 𝐼2 = 𝑥100
0.2100 g
𝑔 𝐼2 = 𝟖𝟎. 𝟖𝟑% 𝒐𝒇 𝑰𝟐 ; 𝒚𝒆𝒔 𝒊𝒕 𝒄𝒐𝒏𝒇𝒐𝒓𝒎𝒔
9) A sample of cod liver oil was analyzed:
a. A 2.487 g sample was dissolved in
the mixture of alcohol and ether
which was neutralized by 0.053N
NaOH. The resulting solution was
heated under reflux condenser and
cooled. It was titrated with 1.8 mL of
0.053N NaOH
(56.11 𝑚𝑔/𝑚𝐸𝑞)(1.8 mL )(0.053N )
𝐴𝑉 =
2.487 g
𝐴𝑉 = 𝟐. 𝟏𝟓𝟐 𝒎𝒈/𝒈; 𝒚𝒆𝒔, 𝒊𝒕 𝒄𝒐𝒏𝒇𝒐𝒓𝒎𝒔
𝑁1 𝑉1 = 𝑁2 𝑉2
(0.053N )(1.8 mL) (0.1𝑁)𝑉2
= e. Does the sample conform with the
0.1𝑁 0.1𝑁
0.954 𝑚𝐿 = 𝑉2
0.954 𝑚𝐿
𝐴𝑉 = 𝑥2
2.487 g
𝐴𝑉 = 𝟎. 𝟕𝟔𝟕𝟐 𝒎𝑳 𝒐𝒇 𝟎. 𝟏𝐍 𝐍𝐚𝐎𝐇
b. A 0.1294 g sample was dissolve in
𝐶𝐶𝑙3 . Twenty-five mL of ICl was
added, stoppered and allowed to
stand for 30 minutes. KI was added
and titrated with 8.9 mL of 0.0994N
Sodium thiosulfate. The blank test
consumed 24 mL of the titrant.
𝐼2 = 127 𝑔/𝑚𝑜𝐿
= 127/1(1000)
𝐼2 = 0.127 𝑔/𝑚𝐸𝑞
𝑥100
(𝑚𝐿 𝑜𝑓 𝑏𝑙𝑎𝑛𝑘 − 𝑚𝐿 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒)(𝑁)(𝑚𝐸𝑞)
𝑔 𝐼2 = 𝑥100
𝑤𝑡. 𝑜𝑓 𝑠𝑥.
(24 mL − 8.9 mL )(0.0994N)(0.127 𝑔/𝑚𝐸𝑞)
𝑔 𝐼2 = 𝑥100
0.1294 g
𝑔 𝐼2 = 𝟏𝟒𝟕. 𝟑𝟏%; 𝒚𝒆𝒔, 𝒊𝒕 𝒄𝒐𝒏𝒇𝒐𝒓𝒎𝒔
c. A 5.09 g sample was treated with
KOH dissolved in alcohol and heated
under a reflux condenser. The ether
extract was evaporated to dryness
on a water bath. The residue left is
1.053 g
𝑤𝑡. 𝑜𝑓 𝑟𝑒𝑠𝑖𝑑𝑢𝑒
% 𝑈𝑛𝑠𝑎𝑝𝑜𝑛𝑖𝑓𝑖𝑎𝑏𝑙𝑒 𝑀𝑎𝑡𝑡𝑒𝑟 = 𝑥100
𝑤𝑡. 𝑜𝑓 𝑠𝑥.
1.053 g
% 𝑈𝑛𝑠𝑎𝑝𝑜𝑛𝑖𝑓𝑖𝑎𝑏𝑙𝑒 𝑀𝑎𝑡𝑡𝑒𝑟 = 𝑥100
5.09 g
% 𝑈𝑛𝑠𝑎𝑝𝑜𝑛𝑖𝑓𝑖𝑎𝑏𝑙𝑒 𝑀𝑎𝑡𝑡𝑒𝑟
= 𝟐𝟎. 𝟔𝟗%; 𝒏𝒐 𝒊𝒕 𝒅𝒐𝒆𝒔 𝒏𝒐𝒕 𝒄𝒐𝒏𝒇𝒐𝒓𝒎
d. A 1.525 g sample was refluxed with
25 mL of 0.5N KOH and required
15.7 mL of 0.51N HCl. Blank
determination consumed 26 mL of
the same acid solution
𝑆𝑉
(𝑚𝐿 𝑜𝑓 𝐻𝐶𝑙𝑏𝑙𝑎𝑛𝑘 − 𝑚𝐿 𝑜𝑓 𝐻𝐶𝑙𝑠𝑎𝑚𝑝𝑙𝑒 )(𝑁)(56.11 𝑚𝑔/𝑚𝐸𝑞)
=
𝑤𝑡. 𝑜𝑓 𝑠𝑥.
(26 mL − 15.7 mL )(0.51N)(56.11 𝑚𝑔/𝑚𝐸𝑞)
𝑆𝑉 =
1.525 g
𝑆𝑉 = 𝟏𝟗𝟑. 𝟐𝟖; 𝒏𝒐, 𝒊𝒕 𝒅𝒐𝒆𝒔 𝒏𝒐𝒕 𝒄𝒐𝒏𝒇𝒐𝒓𝒎
specs?
 i. AV = NMT 1 mL of 0.1N
NaOH in 2 g of sample
ii. SV = 180-192
iii. IV = 145-180
iv. UM = NMT 1.3%
 PHAN111LEC_WEEK 14 ▪ Propionic
▪ Butyric
▪ Valeric
Analysis of Volatile Oils ▪ Benzoic
• A.k.a. Ethereal Oils or Essential Oils or ▪ Cinnamic
Essences ▪ Hydrocyanic
• Odorous compounds found in plants, o Acids in combination with alcohols
distinct odor, optically active, exposure in air as esters
they oxidize ▪ Linalyl acetate
• Contains ▪ Bornyl acetate
o Hydrocarbons of the isocyclic series ▪ Methyl acetate
such as: o Sulfur compounds
▪ Monoturpenes ( C10H16) ▪ Allyl isothiocyanate
▪ Sesquiturpenes (C15H24) • Purity and quality can be judged to some
• Pinene extent by their appearance, odor, color, etc.
• Camphene but the information gained from the
• Limonene determination of their physical constants
• Bronylene
• Fenchene Physical Content
• Dipentene • Specific Gravity – determined by Westphal
• Sylvestrene Balance or Pycnometer that ranges from
• Phellandrene 0.84 to 1.2
o Alcohols both in free state and in o Oils lighter than water: orange,
combination with acids as esters caraway, coriander, lemon,
▪ Cyclic turpentine, and rosemary oils
▪ Monocylic o Oils heavier than water: anise,
• linalool cinnamon, clove, sassafras oils
• Geraniol • Rotatory Power – measured by Laurent
• Citroneol Half-Shadow Polarimeter
• Terpineol o Presence of adulterants such as
• Borneol alcohol or turpentine oil is
• Menthol determined by its influence in the
• Santalool rotatory power values
o Aldehydes • Refractive Index – most used instrument is
▪ Benzaldehyde the Abbe Refractometer that ranges from
▪ Cinnamic aldehyde 1.46 to 1.61 at 20 degC. The determination
▪ Salicylic aldehyde may serve in the detection of extraneous
▪ Citral matter
▪ Citronellal • Congealing Point – most essential oils
o Ketones solidify only at low temp.; low congealing
▪ Camphor point = has impurities
▪ Carvone • Distilling Range
▪ Fenchone o Fractional Distillation – fractionation
▪ Thujone of the oil determines the possible
▪ Menthone presence of alcohol which distills or
o Phenols boils below 100 degC
▪ Anethol • Solubility – generally, volatile oils are soluble
▪ Eugenol in organic solvents (70-90% alcohol);
▪ Carvacrol turpentine oil, petroleum oil or fatty oils are
▪ Saffrol only slightly soluble and can be seen through
▪ Chavicol its turbidity
o Acids sometimes in the free state in
small quantities like Factors causing Deterioration of Volatile Oils
▪ Acetic
• When exposed to light and air, fragrance is
lost
• Terpene-containing oils produces peroxides,
the presence of which indicated by the
whitening of the cork of their containers
• On long standing, volatile oils thicken,
become resinified or deposit crystalline
compounds
• Tin containers promote deterioration of
odor and development of color; should be
an amber-colored bottle
• Adding 5-10% fixed oils or alcohol can
preserve volatile oils
Isolation of Volatile Oils
• Isolations of volatile oils from crude drugs or
oleoresins occur through Steam Distillation
and the measurement of the volume of oil
obtained
• Condenser is combined with the receiver to
avoid as much as possible the loss of volatile
oil vaporization and to provide direct
reading of the volume of oil
• Oil is the drug to be assayed is lighter than
water, its volume is directly measured in the
receiver which is provided with a lower
portion graduated to tenths of a millimeter
• Oil is heavier than water, the oil is
transferred to a measuring cylinder and the
water with whatever oil remains is placed in
a separator
• The oil trap is rinsed with ether, the rinsing
added to the separatory funnel. The ethereal
layer separated is allowed to stand so that
the ether is evaporated, and any oil left is
added to the oil in the measuring cylinder.
The volume of the oil is measured at 25
degC. If the amount of oil is to be expressed
in weight it is dried with anhydrous sodium
sulfate and its specific gravity determined at
25 degC after measuring its volume.
• Clevenger Apparatus – only official USP
method used in quality control of volatile
oils through boiling, condensing, and
decantation
Isolation of Volatile Oil in Spirits
• The assay for volatile oils in spirits is based
on the isolation of the oil from the other
components of the spirit by the use of an
immiscible solvent and measuring the
volume of the liberated oil.
• The contents of the bottle are mixed by
rotating the bottle and treated with more
calcium chloride solution until the oil that
separates is brought to the level of the
graduations on the neck of the flask. The
mixture is centrifuged for 5 minutes at about
1500 revolutions per minute and the volume
of the oil is measured using the calibrations
in the neck of the flask.
• The oil in the spirit is salted out of the
solution by the addition of the saturated
calcium chloride solution. The kerosene
dissolves the oil.
• The HCl is added to neutralize any alkali
which would otherwise made the acids and
aldehydes in the oil will be water soluble
• The Babcock Bottle is provided with a long
neck calibrated into eight divisions of 0.2
mL each
• The percent of oil in the spirit is calculated
as follows:
If the height of the column of the oil-kerosene mixture
occupies 7.5 divisions, thus, the oil will measure 2.5
divisions
7.5 𝑑𝑖𝑣 − 5 𝑑𝑖𝑣. = 2.5 𝑑𝑖𝑣
The 5 divisions represent 1 ml of kerosene added since
each division is equal to 0.2 mL + 1 for error
2.5 𝑑𝑖𝑣 𝑥 0.21 𝑚𝐿 = 0.525 𝑚𝐿
The number of divisions is multiplied by 0.21 instead of
0.2 to correct for the error due to the solubility of the
oil-kerosene layer in the aqueous layer and also due to
contraction of volume of the immiscible solvents when
mixed.
0.525
% 𝑜𝑓 𝑉𝑂 𝑖𝑛 𝑠𝑝𝑖𝑟𝑖𝑡𝑠 = 𝑥 100
5
 % 𝑜𝑓 𝑉𝑂 𝑖𝑛 𝑠𝑝𝑖𝑟𝑖𝑡𝑠 = 10.5%
Determination of Alcohol Content
• Menthol and borneol are the alcohols
present in peppermint oil and rosemary oil
are found free and combined as esters. The
alcohol content determination is so valuable
that it alone is sufficient to prove the purity
and value of the volatile oil
• Determination consists of conversion of the
free alcohol to its acetate ester and
saponification of freshly produces acetate,
and original acetate with standard alcoholic
potassium hydroxide
Isolation of Alcohol Content
• The acetylized oil is allowed to separate
from the aqueous layer
• The water layer is rejected and the oil
washed with several portions of Sodium
carbonate TS. It is then diluted with an equal
volume of water until the last washing is
already alkaline to HPH TS
• The acetylized oil is dried with anhydrous
sodium sulfate. Transfer 5 mL of the dry
acetylized oil to a tared 100 mL Erlenmeyer
flask and weigh accurately
• Add 50 mL of 0.5N alcoholic KOH, connect
the flask with a reflux condenser and boil
the mixture on a water bath for exactly one
hour
• Allow the mixture to cool and add 10 drops
of HPH TS and titrate the excess alkali with
0.5N H2SO4. A blank determination is
performed
• The acetylization flask should be heated
over an asbestos board to avoid the
decomposition of oil
• The acetylization flask is provided with an
air condenser to condense any vapors of the
volatile oil and the acetic acid that is
produced
𝐴 𝑥 7813
%𝑡𝑜𝑡𝑎𝑙 𝑒𝑠𝑡𝑒𝑟 = 𝑥[1 − (𝐸 𝑥 0.0021)
𝐵 − (𝐴 𝑥 0.021)
Where A is the difference between mL of sulfuric acid
in blank and sample, B is the weight of acetylized oil,
and E is the percentage of esters calculated as
menthyl acetate;
• 1 mL of 0.5N KOH is equivalent to 0.07813 g
of menthol
• 1 mL of 0.5N KOH is equivalent to 0.021 g of
acetyl radical
• 1 – (E x 0.0021) is a correction factor which
should be done when the sample of volatile
contains both ester and alcohol
• The value 0.0021 is derived from the ratio of
the acetyl radical to that of methyl acetate
Determination of Aldehyde and Ketone Content
• Bisulfate Method – principle of aldehydes
and ketones forming soluble addition
products with sodium sulfite with water that
leaves a certain volume of oil which do not
contain aldehydes or ketones; measured in
acacia flask
• Hydroxylamine Method – for ketones only
• By finding the difference between the
volume of original oil and that of the residual
oil, the volume of aldehyde or ketone is
determined
• Limited only for the assay of volatile oils
which do not contain constituents other
than aldehyde and ketones or for samples
with very little aldehyde content
𝑉 𝑜𝑓 𝑠𝑥. −𝑉 𝑜𝑓 𝑟𝑒𝑠𝑖𝑑𝑢𝑒
% 𝑉𝑜𝑙 𝑜𝑖𝑙 = 𝑥100
𝑉 𝑜𝑓 𝑠𝑥.
Determination of Phenol Content
• Volatile oils that contain phenols, when
shaken with solution of KOH diminish in
volume because of the steady solubility of
the phenol constituents in alkali leaving the
non-phenolic portion of the oil undissolved
Practice
1) What would be the percentage in VO in
orange spirit if the number of the divisions
occupied by the oil-kerosene mixture is 8
and the volume of kerosene added is 1.2 mL.
The volume of the sample of orange spirit
transferred to the Bobcock bottle is 4.8 mL.
Compute for the percentage volatile oil if
the volume of kerosene is equivalent to 5
divisions.
8 𝑑𝑖𝑣 − 5 𝑑𝑖𝑣. = 3 𝑑𝑖𝑣
3 𝑑𝑖𝑣 𝑥 0.21 𝑚𝐿 = 0.63 𝑚𝐿
0.63 𝑚𝐿
% 𝑜𝑓 𝑉𝑂 𝑖𝑛 𝑠𝑝𝑖𝑟𝑖𝑡𝑠 = 𝑥 100
5
% 𝑜𝑓 𝑉𝑂 𝑖𝑛 𝑠𝑝𝑖𝑟𝑖𝑡𝑠 = 𝟏𝟐. 𝟔%
 2) Exactly 10 mL of cinnamon oil was
introduced into a cassia flask and into it
added was 50 mL of saturated sodium sulfite
solution, boiled and shaken repeatedly. The
undissolved oil remaining after this
treatment measured 4.3 mL. What is the
percentage of cinnamon aldehyde in the
sample?

𝑉 𝑜𝑓 𝑠𝑥. −𝑉 𝑜𝑓 𝑟𝑒𝑠𝑖𝑑𝑢𝑒
% 𝑉𝑜𝑙 𝑜𝑖𝑙 = 𝑥100
𝑉 𝑜𝑓 𝑠𝑥.
10 mL − 4.3 mL
% 𝑉𝑜𝑙 𝑜𝑖𝑙 = 𝑥100
10 𝑚𝐿
% 𝑉𝑜𝑙 𝑜𝑖𝑙 = 𝟓𝟕% 𝒐𝒇 𝒄𝒊𝒏𝒏𝒂𝒎𝒐𝒏 𝒂𝒍𝒅𝒆𝒉𝒚𝒅𝒆

3) 2 mL of benzaldehyde was treated with 25

mL of hydroxylamine HCl and then titrated
with 23 mL of 0.98N NaOH. In the blank
test, the same amount of hydroxylamine
HCL consumed 15 mL of 0.98N NaOH.
Compute for the percentage benzaldehyde if
1 mL of 1N NaOH is equivalent to 106.1 mg
of benzaldehyde

𝑡𝑖𝑡𝑒𝑟 = 𝑁(𝑚𝐸𝑞)
𝑡𝑖𝑡𝑒𝑟 𝑁(𝑚𝐸𝑞)
=
𝑁 𝑁
𝑡𝑖𝑡𝑒𝑟
= 𝑚𝐸𝑞
𝑁

0.1061 g
𝑚𝐸𝑞 =
1N
𝑚𝐸𝑞 = 0.1061 𝑚𝐸𝑞

= (𝑚𝐿 𝑜𝑓 𝑁𝑎𝑂𝐻𝑠𝑎𝑚𝑝𝑙𝑒 − 𝑚𝐿 𝑜𝑓 𝑁𝑎𝑂𝐻𝑏𝑙𝑎𝑛𝑘 )(𝑁)(0.1061)

%𝑏𝑒𝑛𝑧𝑎𝑙. 𝑥100
𝑤𝑡. 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
(23 mL − 15 mL)(0.98N)(0.1061)
%𝑏𝑒𝑛𝑧𝑎𝑙. = 𝑥100
2 mL
%𝑏𝑒𝑛𝑧𝑎𝑙. = 𝟒𝟏. 𝟓𝟗%