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ASSAY OF ALKALOID AND AMINE DRUGS

ALKALOIDS
1. Obtained from plant, animal and synthetic sources
2. Contain organic nitrogen(s) within their chemical structure
3. Possess physiological activity

GENERAL PRINCIPLES
1.) Class of medicinal agents
2.) Slight deficiency of alkaloid
3.) Slight excess

ASSAY OF ALKALOIDAL DRUGS AND PREPARATIONS


1.Standardization
2.Proof of purity
3.Commercial evaluation/ Pharmacolegal purposes

METHODS
1. Gravimetric
2. Volumetric
3. Spectrometric
4. Electrometric
5. Physiological

The amount of alkaloids in a crude drug have considerable variation in different samples of the same drug. Variations is caused by several
factors:
1. The age of the plant collected
2. Season of the year when the drug harvested
3. Soil and climate where the drug grown
4. Conditions under which the drug is collected, dried and stored

Quantity of alkaloids present in Galenical preparations is also subject to variations


1. Quality of drug employed
2. Menstruum used in the extraction of the alkaloid
3. Amount of decomposition of the alkaloid during the process of extraction and storage

Deterioration of alkaloidal preparation:


1. Nature of the alkaloid
2. pH value of preparation
3. heat
4. light

Principle involved in quantitative determination of alkaloids by chemical methods:


(based upon physical and chemical properties of the substance)
PHYSICAL PROPERTIES
SOLUBILITY
1. Alkaloids (R3N) or free alkaloids
-sparingly soluble: water
-soluble: most organic solvents
2. Alkaloidal salts
-soluble: water
-sparingly soluble: immiscible solvents

CHEMICAL PROPERTIES
REACTIONS IN ACIDS AND BASES
1. Alkaloids combine directly with acids to form salts
2. Alkaloids are liberated from aqueous solutions of their salts by alkalis
3. Alkaloids form highly insoluble precipitates with a considerable number of reagents

SOURCES OF ERROR
1. Failure to secure complete extraction of the alkaloids from the drug or from solution
2. Loss of volatile solvent during maceration of the drug before the aliquot portion is taken
3. Imperfect separation of the immiscible liquids
4. Failure to wash the stems of separators and funnels, graduates and other apparatus with solvent
5. Decomposition of the alkaloids
6. Use of the wrong indicator
7. Other sources of error

CHOICES OF INDICATORS FOR ALKALOIDAL TITRATIONS


In alkaloidal assays by volumetric methods, the use of methyl red solution is recommended in all the titrations.

ALKALOIDAL TEST SOLUTIONS


1. Auric chloride
2. Platinic chloride
3. Mercuric chloride
4. Gallotannic acid
5. Picric acid
6. Phosphomolybdic acid
7. Potassium mercuric iodide
8. Mercuric iodide
9. Iodine potassium iodide

MERCURIC IODIDE TS (Valsers reagent) -forms white precipitates with minute traces of many alkaloids when it is added to their acidified
aqueous solutions

IODINE TS
(Wagners reagent) -yields reddish or red-brown precipitates of complex composition with nearly all alkaloids. The precipitates are usually
amorphous. The quantity of reagent used should not be sufficient to color the solution more than a faint yellow.

MERCURIC POTASSIUM IODIDE TS (Mayers reagent) -yields white or slightly yellow precipitates when mixed with dilute solutions of many
alkaloids

Dragendorff's reagent -yields an orange or orange red precipitate

ASSAY PROCEDURE FOR DOSAGE FORMS OF ALKALOIDS AND OTHER AMINE DRUGS
2 major steps:
1. Separation and collection of the amine or alkaloid from other constituents found in the dosage form
2. Analysis of the alkaloid or amine by a suitable analytical method

THEORY OF EXTRACTION
According to NERNSTS LAW if two practically immiscible solvent are in contact and a substance soluble in both liquids is added to them, the
substance will distribute itself between the liquids in such a way that the ratio of the concentrations of the two solutions is a constant
irrespective of the quantity of solute taken. This constant is variously turned the distribution ratio, distribution constant, distribution coefficient,
or partition coefficient.
COMPUTATION: K= C2/C1
where in:
C1- concentration of alkaloid in ether
C2- conc. Of the same alkaloid in equal volume
K- distribution constant or coefficient

Assume that 1 g of atropine in 100 ml of ether soln when shaken with an equal volume of dilute H2SO4 distributes itself so that 0.1g remains
in the ether layer and 0.9 g in the acid layer of the solvent
*in making successive extractions using equal volume of extracting solvents, the following equation is useful in determining the quantity of
solute remaining after n extraction.
V1
FORMULA: Wn=W ( )n
KV 2 +V 2
where
c2
K=
C 1 C2= concentration of solute in the extracting solvent (2)
C1= concentration of solute in the original solvent (1)
W= weight of solute originally taken
Wn= weight of solute remaining in the original solvent after n extractions
V2 and V1= volume of solvents 2 and 1,respectively
n= number of extractions

PROXIMATE AND ULTIMATE ASSAYS


-If the percent of extractive represents the total of a class of plant principles, such as alkaloids or glycosides, etc., the assay is referred to as a
proximate assay.
e.g. the assay of ipecac

-If the percent of extractive from a crude drug represents a single chemical species, such as morphine, the assay is referred to as an ultimate
assay.
e.g. the assay of opium

ASSAY OF CRUDE DRUGS AND GALENICALS


Assay of belladonna leaf

FLUIDEXTRACTS
-Belladonna leaf fluidextract is assayed in a manner similar to the assay of the tincture. The volumes of fluidextract taken as samples are
designated so that approximately 300 mg of the alkaloids will be obtained in the assay residue.
TINCTURES
-Assayed by the same method, except that the amount of the tincture employed as sample is designated so that approximately 0.030 g of the
alkaloids will be obtained in the assay residue
ASSAY OF BELLADONNA TINCTURE
ASSAY OF IPECAC FOR ETHER-SOLUBLE ALKALOIDS

ASSAY OF PHARMACEUTICAL DOSAGE FORMS FOR ALKALOIDAL CONTENT


-Conducted in the same way as the assays of the crude drugs in which the alkaloids occur, except that the method of preparing the samples
for assay differ and the procedures for the purification of the alkaloids are less involved as a rule.
-In the case of capsules and tablets , is to empty about 20 capsules or to powder about 20 tablets and then weigh accurately the amount to
be used in the assay.
ASSAY OF EPHEDRINE SULFATE INJECTION
ASSAY OF AMINOPHYLLINE TABLETS