3H-1,2-二氢-2-(4-甲基苯胺基)甲基-1-吡咯里嗪酮在家兔体内主要代谢产物的研究

用高效液相色谱法对家兔单剂量ig750mg新抗炎镇痛剂3H-1,2二氢-2-(4-甲基苯胺基)-甲基-1-吡咯里嗪酮(Z-47)后尿中的代谢物进行了分离、检测。根据代谢物的色谱行为及与Z-47结构有关的其它药物的代谢途径,推测Z-47羧基衍生物4-(3H-1,2-二氢-1-吡咯里嗪酮-2-甲基胺基)苯甲酸]是一可能的代谢产物,遂用化学方法合成了该衍生物。利用色谱保留值、紫外双波长吸收比值等对代谢物和标准品进行比较,并对尿样的酶水解产物进行色谱分析,证实Z-47羧基衍生物及其酯型β-D-葡糖苷酸结合物是Z-47在家兔体内的主要代谢产物。

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.