Limit Test for Heavy Metals in Pharmaceuticals

The limit for heavy metals is indicated in the individual monographs in terms of ppm, i.e., the parts of lead, Pb, per million parts (by weight) of the substance under examination.

Method A

Standard solution

Into a 50-ml Nessler cylinder pipette 1.0 ml of lead standard solution (20 ppm Pb) and dilute with water to 25 ml. Adjust with dilute acetic acid or dilute ammonia solution to a pH between 3.0 and 4.0, dilute with water to about 35 ml and mix.

Test solution

Into a 50-ml Nessler cylinder place 25 ml of the solution prepared for the test as directed in the individual monograph or dissolve the specified quantity of the substance under examination in sufficient water to produce 25 ml. Adjust with dilute acetic acid or dilute ammonia solution to a pH between 3.0 and 4.0, dilute with water to about 35 ml and mix.

Procedure

To each of the cylinders containing the standard solution and test solution respectively add 10 ml of freshly prepared hydrogen sulphide solution, mix, dilute to 50 ml with water, allow to stand for 5 minutes and view downwards over a white surface; the color produced with the test solution is not more intense than that produced with the standard solution.

Method B

Standard solution. Proceed as directed under Method A.

Test solution

Weigh in a suitable crucible the quantity of the substance specified in the individual monograph, add sufficient sulphuric acid to wet the sample, ignite carefully at a low temperature until thoroughly charred. Add to the charred mass 2 ml of nitric acid and 5 drops of sulphuric acid and heat cautiously until white fumes are no longer evolved. Ignite, preferably in a muffle furnace, at 500° to 600°, until the carbon is completely burnt off. Cool, add 4 ml of hydrochloric acid, cover, digest on a water-bath for 15 minutes, uncover and slowly evaporate to dryness on a water-bath. Moisten the residue with 1 drop of hydrochloric acid, add 10 ml of hot water and digest for 2 minutes. Add ammonia solution dropwise until the solution is just alkaline to litmus paper, dilute to 25 ml with water and adjust with dilute acetic acid to a pH between 3.0 and 4.0. Filter, if necessary, rinse the crucible and the filter with 10 ml of water, combine the filtrate and washings in a 50-ml Nessler cylinder, dilute with water to about 35 ml and mix.

Procedure

Proceed as directed under Method A.

Method C

Standard solution. Into a 50-ml Nessler cylinder pipette 1.0 ml of lead standard solution (20 ppm Pb), add 5 ml of dilute sodium hydroxide solution, dilute with water to 50 ml and mix.

Test solution

Into a 50-ml Nessler cylinder place 25 ml of the solution prepared for the test as directed in the individual monograph, or dissolve the specified quantity of the substance under examination in a mixture of 20 ml of water and 5 ml of dilute sodium hydroxide solution. Dilute with water to 50 ml and mix.

Procedure

To each of the cylinders containing the standard solution and the test solution respectively add 5 drops of sodium sulphide solution, mix, allow to stand for 5 minutes and view downwards over a white surface; the color produced with the test solution is not more intense than that produced with the standard solution.

Method D

Standard solution

Into a small Nessler cylinder pipette 10.0 ml of either lead standard solution (1 ppm Pb) or lead standard solution (2 ppm Pb).

Test solution

Prepare as directed in the individual monograph and pipette 12 ml into a small Nessler cylinder.

Procedure

To the cylinder containing the standard solution add 2.0 ml of the test solution and mix. To each of the cylinders add 2 ml of acetate buffer pH 3.5, mix, add 1.2 ml of thioacetamide reagent, allow to stand for 2 minutes and view downwards over a white surface; the color produced with the test solution is not more intense than that produced with the standard solution.

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