Enantioselective analysis of levetiracetam and its enantiomer R-alpha-ethyl-2-oxo-pyrrolidine acetamide using gas chromatography and ion trap mass spectrometric detection

A gas chromatographic-mass spectrometric method was developed for the enant ioselective analysis of levetiracetam and its enantiomer (R)-alpha-ethyl-2- oxo-pyrrolidine acetamide in dog plasma and urine. A solid-phase extraction procedure was followed by gas chromatographic separation of the enantiomer s on a chiral cyclodextrin capillary column and detection using ion trap ma ss spectrometry. The fragmentation pattern of the enantiomers was further i nvestigated using tandem mass spectrometry. For quantitative analysis three single ions were selected from the enantiomers, enabling selected ion moni toring in detection. The calibration curves were linear from 1 mu M to 2 mM for plasma samples and from 0.5 mM to 38 mM for urine samples. In plasma a nd urine samples the inter-day precision, expressed as relative standard de viation was around 10% in all concentrations. Selected ion monitoring mass spectrometry is suitable for quantitative analysis of a wide concentration range of levetiracetam and its enantiomer in biological samples. The method was successfully applied to a pharmacokinetic study of levetiracetam and ( R)-alpha-ethyl-2-oxo-pyrrolidine acetamide in a dog. (C) 2000 Elsevier Scie nce B.V. All rights reserved.