Pilocarpine hydrochloride in ophthalmic solutions: modification of a high-pressure liquid chromatographic determination and survey.

Pilocarpine undergoes 2 important reactions in solutions, epimerization to isopilocarpine and hydrolysis to pilocarpic acid. There is no official USP limit for isopilocarpine or pilocarpic acid in pilocarpine hydrochloride ophthalmic solutions. An existing high-pressure liquid chromatographic (HPLC) method was modified by changing the buffer system to permit its use with constant-pressure as well as constant-volume instruments. The procedure separates all 3 components on a cation exchange resin; pilocarpine and isopilocarpine are determined directly and pilocarpic acid indirectly. Ophthalmic solutions and drug substances were obtained from substantially all the United States marketers of pilocarpine opthalmic solutions and were analyzed by the modified HPLC method. Results of the survey show that isopilocarpine is present to the extent of 0.4-3% and pilocarpic acid at levels of 0.6-7% of total alkaloid.