Validation of a high-performance liquid chromatographic method for the enantiospecific quantitation of zopiclone in plasma

Zopiclone is a hypnosedative with clinical effects similar to benzodiazepines but thought to have less potential for rebound insomnia and withdrawal effects. Zopiclone is administered as a racemic mixture, and an enantiospecific method of analysis of zopiclone in plasma is desirable in the study of pharmacokinetic drug interactions. We report a modification of an HPLC method reported by Foster et al. using a closely related structural analogue of zopiclone as internal standard. Zopiclone was detected at 306 nm and linear calibration curves were constructed in the range of 1.0–250 ng/mL for each enantiomer. The % CV at 2.5 ng/mL was 12.0% for (−)‐zopiclone and 14.3% for (+)‐zopiclone, and the limit of quantification of each enantiomer was 2.5 ng/mL. At higher concentrations, the coefficient of variation was less than 10%. The nominal concentration of quality control samples was predicted with an accuracy within a range of ±11.6%. The method was used in the analysis of plasma obtained from psychiatric patients. One sample obtained following a non‐fatal overdose with zopiclone contained the metabolites (−)‐N‐oxide zopiclone and both enantiomers of desmethyl zopiclone. The metabolite enantiomers were resolved on the column with retention times similar to zopiclone. The N‐oxide metabolite co‐eluted with internal standard. Copyright © 2002 John Wiley & Sons, Ltd.