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Validation of a high‐performance liquid chromatographic method for the enantiospecific quantitation of zopiclone in plasma
Author(s) -
Gebauer Markus G.,
Alderman Christopher P.
Publication year - 2002
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.135
Subject(s) - zopiclone , chemistry , metabolite , chromatography , enantiomer , pharmacokinetics , high performance liquid chromatography , active metabolite , pharmacology , hypnotic , stereochemistry , biochemistry , medicine
Abstract 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.