STUDY ON MAJOR METABOLITES OF 3H-1,2-DIHYDRO-2-(4-METHYLPHENYLAMINO)-METHYL-1-PYRROLIZINONE IN RABBITS

The metabolites of a 750 mg oral dose of Z-47 3H-1,2-dihydro-2(4-methylphenylamino)methyl-1-pyrrolizinone,a new anti-inflammatory and analgesic agent,in rabbiturine were separated and detected with high performance liquid chromatographic methed.On basis ofthe chromatographic behavior of Z-47 metabolites and biotransformation pathways of drugs with partialstructure of Z-47,the carboxylic derivative of Z-47 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methylamino)benzoic acid was proposed as a potential metabolite so that the compound wassynthesized.The authentic substance was then compared with one of the metahalites by thechromatographic retention time and the ratio of their UV-absorbances at two wavelengths.Theenzyme-hydrolyzed product of another metabolite was also analysed.It was consequently confirmedthat the carboxylic derivative of Z-47 and its acyl β-D-glucuronide are major metabolits of Z-47 inrabbits.