摘要
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。
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.
出处
《药学学报》
CSCD
北大核心
1996年第11期855-860,共6页
Acta Pharmaceutica Sinica
基金
国家自然科学基金
关键词
吡咯里嗪酮
合成
甲基苯胺基
消炎镇痛药
H-1
2-dihydro-2-(4-methylphenylamino)methyl-1-pyrrolizinone(Z-47)
Metablite
4-(3H-1
2-dihydro-1-pyrrolizinone-2-methyl-amino)-benzoic acid(carboxylic derivative ofZ-47)
Acyl β-D-glucuronide
High performance liquid chromatography
