title: Validation of a high-performance liquid chromatographic method for the enantiospecific quantitation of zopiclone in plasma.
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.
authors.affiliation: Pharmacy Department, Repatriation General Hospital, Daw Park, Adelaide, South Australia 5041, Australia. Markus.Gebauer@rgh.sa.gov.au
authors.forename: Markus G
authors.initials: MG
authors.lastname: Gebauer
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Alderman
mesh_terms: D053961:Azabicyclo Compounds; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006993:Hypnotics and Sedatives / Q000097:blood*; D010879:Piperazines / Q000097:blood*; D012015:Reference Standards; D013237:Stereoisomerism
chemical_list: D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; C515050:zopiclone