Penicillamine Tablets

General Notices

Action and use

Disease-modifying antirheumatic drug; chelating agent; treatment of Wilson’s disease; heavy metal poisoning; cystinuria.

Definition

Penicillamine Tablets contain Penicillamine. They are coated.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of penicillamine, C5H11NO2S

95.0 to 105.0% of the stated amount.

Identification

A. Shake a quantity of the powdered tablets containing 20 mg of Penicillamine with 4 mL of water and filter. Add to the filtrate 2 mL of phosphotungstic acid solution and allow to stand for a few minutes. A deep blue colour is produced.
B. Dissolve a quantity of the powdered tablets containing 10 mg of Penicillamine in 5 mL of water and add 0.3 mL of 5m sodium hydroxide and 20 mg of ninhydrin. An intense blue or violet-blue colour is produced immediately.

Tests

Mercuric salts

Not more than 10 ppm, calculated with reference to the content of penicillamine, when determined by the following method. Disperse a quantity of the powdered tablets containing 1 g of Penicillamine in 10 mL of water in a stoppered flask, add 0.2 mL of 9m perchloric acid and swirl to dissolve. Add 1 mL of ammonium pyrrolidinedithiocarbamate solution, mix, add 2 mL of 4-methylpentan-2-one, shake well for 1 minute and add sufficient water to produce 25 mL. Determine by atomic absorption spectrophotometry, Appendix II D, introducing the methylpentanone layer into the flame, measuring at 254 nm and using 4-methylpentan-2-one in place of water. Use mercury standard solution (10 ppm Hg) for the standard solutions, adjusted to contain the same concentrations of 9m perchloric acid, ammonium pyrrolidinedithiocarbamate solution and 4-methylpentan-2-one as the solution being examined.

Penicillamine disulfide

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Shake a quantity of the powdered tablets containing 40 mg of Penicillamine with 10 mL of the mobile phase, filter and use the filtrate.
(2) 0.004% w/v of penicillamine disulfide EPCRS in the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography (5 µm) (Lichrospher 5 C8 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 220 nm.
(f) Inject 20 µL of each solution.
mobile phase

0.01% w/v of disodium edetate and 0.2% w/v of methane sulfonic acid.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to penicillamine disulfide is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1.0%).

Assay

Weigh and powder 20 tablets. Dissolve a quantity of the powder containing 0.1 g of Penicillamine as completely as possible in 50 mL of water and filter. Add to the filtrate 5 mL of 1m sodium hydroxide and 0.2 mL of a 0.1% w/v solution of dithizone in ethanol (96%) and titrate with 0.02m mercury(ii) nitrate VS. Each mL of 0.02m mercury(ii) nitrate VS is equivalent to 5.968 mg of C5H11NO2S.