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

Autor: Christopher P Alderman, Markus G Gebauer
Rok vydání: 2002
Předmět:
Zdroj: Biomedical Chromatography. 16:241-246
ISSN: 1099-0801
0269-3879
Popis: 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.
Databáze: OpenAIRE