Chromatographic separation of piracetam and its metabolite in a mixture of microsomal preparations, followed by an MS/MS analysis

作者：Sahu Kapendra; Siddiqui Anees A^*; Shaharyar Mohammad; Ahmad Niyaz; Anwar Mohammad; Ahmad Farhan J

来源：European Journal of Medicinal Chemistry, 2013, 65: 94-101.

DOI：10.1016/j.ejmech.2013.04.053

• Piracetam metabolism
• Human liver microsomes
• Metabolic pathway
• Pharmacokinetics of the generated metabolite
• UPLC-MS/MS
• Validation

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).

• 出版日期2013-7