title: Enantioselective HPLC determination of oxiracetam enantiomers and application to a pharmacokinetic study in beagle dogs.
abstract: An enantioselective high-performance liquid chromatography method was developed and validated for the determination of oxiracetam enantiomers, a cognition and memory enhancer, in beagle dog plasma. The plasma samples were prepared by methanol extraction from 200μL plasma, and then the baseline resolution was achieved on a Chiralpak ID column (250mm×4.6mm, 5μm) with mobile phase of hexane-ethanol-trifluoroacetic acid (78:22:0.1, v/v/v) at flow rate of 1.0mL/min. The column elute was monitored using ultraviolet detection at 214nm. The method was linear over concentration range 0.50-100μg/mL for both enantiomers. The relative standard deviation values for intra- and inter-day precision were 0.78-13.61 and 0.74-8.92% for (R)- and (S)-oxiracetam, respectively. The relative error values of accuracy ranged from -4.74 to 10.48% for (R)-oxiracetam and from -0.19 to 11.48% for (S)-oxiracetam. The method was successfully applied to a pharmacokinetic study of individual enantiomer and racemic oxiracetam in beagle dogs after oral administration. The disposition of the two enantiomers was not stereoselective and chiral inversion was not observed in beagle dogs. The pharmacokinetic profiles of (S)-oxiracetam were similar with racemic oxiracetam in beagle dogs.
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Jiangsu, China.
authors.forename: Qiuyang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Jiangsu, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Jiangsu, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Jiangsu, China.
authors.forename: Junxiu
authors.initials: J
authors.lastname: Li
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Jiangsu, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Jiangsu, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Jiangsu, China.
authors.forename: Jiake
authors.initials: J
authors.lastname: He
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Jiangsu, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Jiangsu, China. Electronic address: chenxj-lab@hotmail.com.
authors.forename: Xijing
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D004355:Drug Stability; D018697:Nootropic Agents / Q000097:blood* / Q000737:chemistry* / Q000493:pharmacokinetics; D011759:Pyrrolidines / Q000097:blood* / Q000737:chemistry* / Q000493:pharmacokinetics; D013237:Stereoisomerism
chemical_list: D018697:Nootropic Agents; D011759:Pyrrolidines; C040619:oxiracetam
keywords: Enantiomer; Oxiracetam; Pharmacokinetics; Racemate; Stereoselective HPLC