Enantioselective analysis of zopiclone in rat brain by liquid chromatography tandem mass spectrometry

A new high-performance liquid chromatographic method with triple quadrupole mass spectrometry detection was developed and validated for the quantification of zopiclone enantiomers in rat brain samples. Zopiclone enantiomers were resolved on a CHIRALPAK AD column with a mobile phase consisting of acetonitrile/ethanol/methanol (60:20:20, v/v/v) at a flow rate of 1.3 mL min(-1). Moclobemide was used as internal standard. The sample treatment procedure was carried out employing solid-phase extraction, yielding mean absolute recoveries of 89.6 and 91.7% for each zopiclone enantiomer. The validated method showed linearity in the range of 0.29-344.8 ng g(-1), with quantification limits of 0.29 ng g(-1) for both enantiomers. Precision and accuracy were within acceptable levels of confidence (<15%). The method was applied in a pilot study of zopiclone kinetic disposition in rats. It could be observed that the levels of (+)-(S)-zopiclone were always higher than those of (-)-(R)-zopiclone, confirming the stereoselective disposition of zopiclone.