Chromatographic separation of piracetam and its metabolite in a mixture of microsomal preparations, followed by an MS/MS analysis
Chromatographic separation of piracetam and its metabolite in a mixture of microsomal preparations, followed by an MS/MS analysis
复制标题
DOI：
10.1016/j.ejmech.2013.04.053
复制
发表时间：
2013-07-01
影响因子：
6.7
通讯作者：
Ahmad, Farhan J.
中科院分区：
文献类型：
--
作者：
Sahu, Kapendra;Siddiqui, Anees A.;Ahmad, Farhan J.
建立了快速超高效液相色谱-串联质谱法（UPLC-MS/MS）同时测定人微粒体制剂中吡拉西坦及其代谢物（M1）的快速生物分析方法。此外，开发了一种经验证的大鼠血浆中M1的方法，并成功应用于药代动力学研究。本研究旨在确定吡拉西坦I相代谢的代谢途径，并使用负责人肝微粒体（HLM）中吡拉西坦代谢的细胞色素P450亚型。同时通过计算机模拟提出了吡拉西坦的其他潜在代谢物。所得2-（2-氧代吡咯烷-1-基）乙酸是微粒体处理后检测到的唯一代谢产物。酰胺水解主要形成代谢物，即，2-（2-氧代吡咯烷-1-基）乙酸（M1）。(C)2013年Elsevier Masson SAS。All rights reserved.
A rapid bioanalytical method was evaluated for the simultaneous determination of piracetam and its metabolite (M1) in human microsomal preparations by fast ultra-performance liquid chromatography/ tandem mass spectrometry (UPLC-MS/MS). In addition, a validated method of M1 in rat plasma was developed and successfully applied on pharmacokinetic studies. The present study was carried out to determine the metabolic pathways of piracetam for phase I metabolism and used cytochrome P450 isoforms responsible for the piracetam metabolism in human liver microsomes (HLMs). While additional potential metabolites of piracetam were suggested by computer-modeling. The resulting 2-(2-oxopyrrolidin-1-yl) acetic acid was the sole metabolite detected after the microsomal treatment. The amide hydrolysis mainly underwent to form a metabolite i.e., 2-(2-oxopyrrolidin-1-yl) acetic acid (M1). (C) 2013 Elsevier Masson SAS. All rights reserved.