OPTICAL RESOLUTION OF IMIDAPRIL HYDROCHLORIDE BY HIGHPERFORMANCE LIQUID-CHROMATOGRAPHY AND APPLICATION TO THE OPTICAL PURITY TESTING OF DRUGS

Imidapril hydrochloride, a newly synthesized angiotensin-converting en zyme (ACE) inhibitor, is administered as a single enantiomer (SSS-form ) because it is the most active of the eight possible optical isomers. Three different approaches to applying high-performance liquid chroma tography (HPLC) were developed for the resolution of optical isomers o f imidapril hydrochloride. One is the reversed-phase HPLC method for t he separation of diastereomers from the enantiomeric pairs of imidapri l. The second method involves the derivatization of imidapril with a c hiral reagent and separation on a silica gel column (normal-phase HPLC ). The last method is the direct separation of enantiomers of imidapri l hydrochloride by using chiral stationary phases (CSPs). These three methods were successfully applied to the optical purity testing of dru g substances and those in tablets. The methods were also used in a sta bility study of imidapril hydrochloride, including its stability in aq ueous solutions, and imidapril tablets.