Comparison of methods for determining penicillamine in bulk drug and formulations.

The mercuric acetate method (Method I) cited in the Code of Federal Regulations (CFR) as the official method for determining the penicillamine content of a drug was compared with a nonaqueous amine titration (Method II), a nonaqueous acid titration (Method III), and a hydroxylamine assay (Method IV). Quantitative determinations were made for 3 types of penicillamine samples: commercial lots of bulk drug, capsules, and test solutions containing known amounts of penicillamine and EDTA. Method III proved unsatisfactory in the bulk drug determinations. Method II, although slightly less precise than Method I, gave generally satisfactory results for the bulk drug and capsule samples. Method IV was the only method to give satisfactory results in the presence of EDTA.