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Limit Tests in Pharmaceuticals


Learn how Limit Tests (Test for Sulphates, Test for Iron, Test for Arsenic, Test for Chlorides) are being carried out in Pharmaceuticals

What is Impurity?

Any material that affects the purity of the material of interest i.e. active ingredient or drug substance.

Definition :

Limits tests are quantitative or semiquantitative tests designed to identify and control small quantities of impurity, which are likely to be present in the substances.

Types:

1.Tests in which there is no visible reaction
2.Comparison methods
3.Quantitative determinations
Dissolve the specified quantity of the substance under test in 30 to 40 ml of water, or, where the substance is already in solution, add water to make a total volume of 30 to 40 ml, and, if necessary, neutralize the solution with nitric acid to litmus. Add 1 ml each of nitric acid and of  silver nitrate TS and sufficient water to make 50 ml. Mix, and allow to stand for 5 minutes protected from direct sunlight. Unless otherwise specified in the monograph, compare the turbidity, if any, with that produced in a solution containing the volume of 0.020 N hydrochloric acid specified in the monograph.

Reaction: 

Cl- +Ag+ --> AgCl¯

Test for Sulphates:

lThe aim of the test is to control the impurity due to sulphate in inorganic substances. The test is based on the precipitation of SO42-, with barium chloride in the presence of hydrochloric acid and traces of barium sulphate. The opalescent solution so obtained is compared with a standard turbidity containing a known amount of SO42ion.
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Procedure:

Dissolve the specified quantity of the substance under test in 30 to 40 mL of water, or, where the substance is already in solution, add water to make a total volume of 30 to 40 mL, and, if necessary, neutralize the solution with hydrochloric acid to litmus. Add 1 mL of 3 N hydrochloric acid, 3 mL of barium chloride TS, and sufficient water to make 50 mL. Mix, and allow to stand for 10 minutes. Unless otherwise specified in the monograph, compare the turbidity, if any, with that produced in a solution containing the volume of 0.020 N sulfuric acid specified in the monograph.

Reaction:

SO42- + Ba2+ --> BaSO4¯

Test for Iron:

The test depends on the formation of a purple colour by reaction of the iron with thioglycollic acid in a solution buffered with ammonium citrate and comparison of the colour produced with a standard colour containing a known amount of iron.

Methodology:

Dissolve the specified quantity of the substance being examined in water, or prepare a solution as directed in the individual monograph, and transfer to a Nessler cylinder. Add 2 ml of a 20% w/v solution of iron-free citric acid and 0.1 ml of thioglycolic acid, mix, make alkaline with iron-free ammonia solution, dilute to 50 ml with water and allow to stand for 5 minutes. Any colour produced is not more intense than that obtained by treating in the same manner 2.0 ml of iron standard solution (20 ppm Fe) in place of the solution being examined.

Reaction:

Reaction in Iron test
 

Test for Arsenic:

The test for arsenic is based on the procedure in which all arsenic if present is converted into arsine (AsH3) by reduction with zinc and hydrochloric acid. The reaction of the issuing gases with mercuric chloride paper producers a yellow stain which can be compared with that produced from a known amount of arsenic.

Apparatus:

The apparatus consists of a 100 ml bottle or conical flask closed with a rubber or ground glass stopper through which passes a glass tube (about 20 cm x 5 mm). The lower part of the tube is drawn to an internal diameter of 1.0 mm, and 15 mm from its tip is a lateral orifice 2 to 3 mm in diameter. When the tube is in position in the stopper the lateral orifice should be at least 3 mm below the lower surface of the stopper. The upper end of the tube has a perfectly flat surface at right angles to the axis of the tube. A second glass tube of surface, is placed in contact with the first and is held in position by two spiral springs or clips. Into the lower tube insert 50 to 60 mg of lead acetate cotton, loosely packed, or a small plug of cotton and a rolled piece of lead acetate paper weighing 50 to 60 mg. Between the flat surfaces of the tubes place a disc or a small square of mercuric chloride paper large enough to cover the orifice of the tube (15 mm x 15 mm)

Method:

Into the bottle or conical flask introduce the test solution prepared as directed in the individual monograph, add 5 ml of 1M potassium iodide and 10 g of zinc AsT. Immediately assemble the apparatus and immerse the flask in a water-bath at a temperature such that a uniform evolution of gas is maintained. After 40 minutes any stain produced on the mercuric chloride paper is not more intense than that obtained by treating in the same manner. 1.0 ml of arsenic standard solution (10 ppm As) diluted to 50 ml with water.  

Reaction:

2AsH3 + HgCl2  -->  Hg(AsH2)2 + 2HCl. Other arsenic salts like
AsH(Hgcl)2, As (HgCl) and As2Hg3


Test for Chlorides:

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Method:

As a pointed out in above two solutions involved are sample solution and standard solution which are prepared as described procedure
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Procedure:

This test is used to limit the amount of chloride as an impurity in inorganic substances. The procedure consists in the precipitation of the chloride from the sample with AgNO3 in the presence of dilute HNO3. The opalescent solution obtained from the sample is compared with a standard opalescence obtained from a known amount of chloride ions.
Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
Email: .moc.enilediugamrahp@ofni Need Help: Ask Question


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