Enantioselective HPLC determination of oxiracetam enantiomers and application to a pharmacokinetic study in beagle dogs

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 200 mu L plasma, and then the baseline resolution was achieved on a Chiralpak ID column (250 mm x 4.6 mm, 5 mu m) with mobile phase of hexane ethanol trifluoroacetic acid (78:22:0.1, v/v/v) at flow rate of 1.0 mL/min. The column elute was monitored using ultraviolet detection at 214 nm. The method was linear over concentration range 0.50-100 mu g/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. (C) 2015 Elsevier B.V. All rights reserved.