title: HPLC-ESI-MS/MS validated method for simultaneous quantification of zopiclone and its metabolites, N-desmethyl zopiclone and zopiclone-N-oxide in human plasma.
abstract: A simple, selective and sensitive isocratic HPLC method with triple quadrupole mass spectrometry detection has been developed and validated for simultaneous quantification of zopiclone and its metabolites in human plasma. The analytes were extracted using solid phase extraction, separated on Symmetry shield RP8 column (150 mm x 4.6 mm i.d., 3.5 microm particle size) and detected by tandem mass spectrometry with a turbo ion spray interface. Metaxalone was used as an internal standard. The method had a chromatographic run time of 4.5 min and linear calibration curves over the concentration range of 0.5-150 ng/mL for both zopiclone and N-desmethyl zopiclone and 1-150 ng/mL for zopiclone-N-oxide. The intra-batch and inter-batch accuracy and precision evaluated at lower limit of quantification and quality control levels were within 89.5-109.1% and 3.0-14.7%, respectively, for all the analytes. The recoveries calculated for the analytes and internal standard were > or = 90% from spiked plasma samples. The validated method was successfully employed for a comparative bioavailability study after oral administration of 7.5 mg zopiclone (test and reference) to 16 healthy volunteers under fasted condition.
authors.affiliation: Department of Chemistry, School of Sciences, Gujarat University, Navrangpura, Ahmedabad 380009, India.
authors.forename: Hiren N
authors.initials: HN
authors.lastname: Mistri
authors.forename: Arvind G
authors.initials: AG
authors.lastname: Jangid
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Pudage
authors.forename: Pranav
authors.initials: P
authors.lastname: Shrivastav
mesh_terms: D053961:Azabicyclo Compounds / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005215:Fasting; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood*; D013058:Mass Spectrometry / Q000379:methods*; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D011786:Quality Control; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; C515050:zopiclone; C053228:zopiclone N-oxide; C053229:N-desmethylzopiclone