Official compounds
It constitute an important section of pharmacopoeia which gives all necessary information of drugs and compounds that are official. The information includes the title, subtitle, molecular formula, molecular weight , test for identification , tests for purity , description and solubility , method of assay , category and dose it applicable
Assay
The quantitative estimation of the amount of drug present in a given sample constitutes as assay. The percentage purity of the sample is determine by caring out its assay
Limit test
These are qualitative or semi- quantitative test designed to detect and limit small quantities of impurities that are commonly present in pharmaceutical substance. They are based on the comparison or opalescence, turbid ty or colour produced due to impurity in asample with that produced in a standard under t he same test conditions
Ex
Limi t test for CCl, SO4, Fe2 , Heavy metals, lead and arsenic
Limit test for arsenic
The limit test for arsenic is provided to demonstrate that the content of arsenic does not exceed the limit given in the individual monograph in terms of micrograms of arsenic per gram of the test substance.
To carry out the limit test for arsenic a solution is prepared from the test substance by a procedure specified in the monograph.
This procedure assures that the solution in every case contains the whole of the arsenic (if any) present in the substance.
The standard stain against which the comparison is made contains 10 μg of As.
The procedure described may also be used to determine the amount of arsenic in the substance by matching the depth of color of the stain with a series of standard stains.
In the statements of arsenic limits, the permitted amount of arsenic is expressed as As.
Limit test for Arsenic
Principle
The principle is based on converting any arsenic impurity present in the sample to arsine gas by a series of reaction. The arsine gas is made to come in contact with mercuric chloride test paper when by it produces a yellow or brown s train due to the formation of mercuric arsenic
The stain produce by the sample is compare to a standard stain produced by standard strain
The sample stain should not be darker than standard stain
Reactions
1. The arsenic impurity is converted in acidic medium into arsenious acid or arsenic acid depending upon the valency state of arsenic
As 3+ -------------------------- As (OH)3 or H3 AsO3
Trivalent Arsenious acid
As 5+ -------------------------- O = As (OH)3 or H3 AsO4
Pentavalent Arsenic acid
2. Any arsenic acid formed is converted int arsenious acid by reduction with stannous chloride and hydro chloric acid
Stanous chloride
H3 ASO4 ------------------------------------ H3ASO3
3. The arsenic acid is further reduced to arsine gas with the help of nacent hydrogen obtained in the reaction between zinc and hydrochloride acid
Reduction
H3ASO3 +6H ---------------------------------------- ASH3 +3H2O
4. Arsenic gas react with mercuric choride test paper to produce yellow to brown stain due to formation of mercuric arsenide
2ASH3 + HGCl2 ----------------------------------- Hg (As H2)2 + 2HCl
Apparatus
It consist of which mouthed bottle of 120ml capacity fitted with a rubber bung.
Through the rubber bung insert a glass tube as a internal diameter of 6.0 mm and external diameter of 8.0 mm
It has a total length of 200 mm , is drawn out at one end to a diameter of about 1 mm, and has a hole not less than 2 mm in diameter blown in the side of the tube, near the constricted part.
The mercuric chloride test paper is placed between the bund and clipped together with a clip
Procedure
The glass tube is packed with lead acetate cotton
Sample Stain
The solution of the sample is placed in the wide mouthed bottle.
10 ml stagnated HCl , and 10 grms of zinc is added to the sample solution.
The reaction is allowed to proceed for 40 minutes at the temperature of 40c
Standard stains
Solutions are prepared by adding to 50 ml of water, 10 ml of stannated hydrochloride acid AsT and quantities of dilute arsenics solution AsT varying 0.2 ml to 1 ml. The resulting solutions , when treated as described in the general test yield stains on the mercuric chloride paper referred to as the standard stains
Stannated hydrochloride acid AsT
Stannous chloride solution AsT - 1ml
Hydrochloric acid AsT - 100 ml
Comparison and results
The intensity of sample stain is immediately compared to the that of the standard stain. For the sample to pass the limit test for arsenic , the intensity of sample stain should not be greater than of the standard stain
Basis of test
Both in the sample and the the standard is done by the combined action of Zinc, acid , stannous chloride and potassium iodide.
The pharmacopoeial test of arsenic which is a toxic component in medicinal substances is based on the fact that arsenic in the arsenious state can be readily reduced to arsine (As H3) gas which passing over mercuric chloride paper develops a yellow to brown stain
The intensity and length of which are proportional to the amount of arsenic
The solution is reacted with a reducing agent like stannous chloride or sulphurous acid to convert the penta valent arsenic acid into the trivalent arsenious acid which is converted into gaseous arseniou hydride (arsine gas) with the help of nascent hydrogen produced by the action of zinc with hydrochloric acid
HCl
Arsenic to arsenious or arsenic acid in presence of acidic media
Stannous chloride
This solution is reacted with a reducing agent like stannous chloride to convert the pentavalent arsenic acid into the trivalent arsenious acid
Zinc with hydrochloric acid
Nascent hydrogen produced by the action of zinc with hydrochloric acid
Trivalent arsenious acid which is converted into gaseous arsenious hydride (arsine gas) with the help of nascent hydrogen produced by the action of zinc with hydrochloric acid
Sn Cl2 Zn + HCl
H3 AsO4 ------------------- H3 AsO3 ----------------- AsH3 + 3H2O
Arsenic acid Arsenious acid Arsine gas
Arsine gas is carried out through the tube with the help of hydrogen to the mercuric chloride paper
The reaction of arsine with mercuric chloride produces a yellow colored stain
The intensity of the color is dependent on the quantity of arsenic
2AsH3 + HgCl2 ------------------------ Hg (AsH2)2 +2HCl
Yellow stain
The most suitable temperature for carrying out the test is generally abou 40c
The tube must be washed with HCl , rinsed with water and dried between successive tests
The stains may be preserved by dipping in hot melted paraffin or placing over phosphorus pentoxide protected from light
Stannous chloride is required for the complete evolution fo arsine
The acion between pure zinc and hydrochloric acid is slow and he presence of other metals accelerates the formation of hydrogen . Stannous salts reduce arsenic to arsenious state
Hydrogen sulphide
Metallic zinc may contain traces of sulphiide which on reaction with the acid yields hydrogen sulphide
The lead acetate papers are used to trap any hydrogen sulphide evolved together with arsine.
The hydrogen sulphide reacts with mercuric chloride paper developing a dark stain , thus interfering with the formation of the required mercuric arsenide stain
Apparatus
A suitable type of apparatus is described below, though other acceptable constructions are available.
A wide-mouthed bottle of about 120 ml capacity, is fitted with a rubber bung through which passes a glass tube.
The tube is passed through the bung fitting the bottle so that, when inserted in the bottle containing 70 ml of liquid, the constricted end of the tube is above the surface of the liquid and the hole in the side is below the bottom of the bung.
The upper end of the tube is cut off square, and is either slightly rounded off or ground smooth.
Two rubber bungs (about 25 mm × 25 mm), each with a hole bored centrally and true and exactly 6.5 mm in diameter, are fitted with a rubber band or spring clip for holding them tightly together.
Alternatively, the two bungs may be replaced by any suitable construction satisfying the conditions of the test, as described below.
Recommended procedure
Pack the glass tube lightly with cotton-wool, previously moistened with lead acetate (80 g/l) TS and dried, so that the upper surface of the cotton-wool is not less than 25 mm below the top of the tube.
Insert the upper end of the tube into the narrow end of one of the pair of rubber bungs, either (1) to a depth of about 10 mm in the case of the tube with the rounded-off end or (2) so that the ground end of the tube is flush with the larger end of the bung. Place a piece of mercuric bromide paper AsR flat on the top of the bung, and place the other bung over it. Secure the assembly by means of a rubber band or spring clip, in such a manner that the borings of the two bungs (or the boring of the upper bung and the glass tube) meet to form a true tube 6.5 mm in diameter interrupted by a diaphragm of mercuric bromide paper AsR.
Instead of this method of attaching the mercuric bromide paper AsR, any other method may be used provided (1) that the whole of the evolved gas passes through the paper, (2) that the portion of the paper in contact with the gas is a circle 6.5 mm in diameter, and (3) that the paper is protected from sunlight during the test.
Place the solution, prepared as specified in the monograph, in the wide-mouthed bottle, add 1 g of potassium iodide AsR and 10 g of granulated zinc AsR, and place the prepared glass tube assembly quickly into position. Allow the reaction to proceed for 40 minutes. Compare any yellow stain that is produced on the mercuric bromide paper AsR, with a standard stain, produced in a similar manner with a known quantity of dilute arsenic AsTS. Make the comparison in daylight and immediately after simultaneous preparation of the test and standard stains; the stains fade on keeping.
The most suitable temperature for carrying out the test is generally about 40°C The temperature may be adjusted to obtain a regular
The reaction may be accelerated by placing the apparatus on a warm surface, care being taken to ensure that the mercuric bromide paper AsR remains quite dry throughout the test.
Between successive tests, the tube must be washed with hydrochloric acid (~250 g/l) AsTS, rinsed with water, and dried.
