title: Chromatographic separation of piracetam and its metabolite in a mixture of microsomal preparations, followed by an MS/MS analysis.
abstract: 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).
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India. kapendra_sahu@yahoo.com
authors.forename: Kapendra
authors.initials: K
authors.lastname: Sahu
authors.forename: Anees A
authors.initials: AA
authors.lastname: Siddiqui
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shaharyar
authors.forename: Niyaz
authors.initials: N
authors.lastname: Ahmad
authors.forename: Mohammad
authors.initials: M
authors.lastname: Anwar
authors.forename: Farhan J
authors.initials: FJ
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008862:Microsomes, Liver / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D010889:Piracetam / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry
chemical_list: D010889:Piracetam
keywords: Human liver microsomes; Metabolic pathway; Pharmacokinetics of the generated metabolite; Piracetam metabolism; UPLC–MS/MS; Validation