Determination of quetiapine and its metabolites in plasma by field-enhanced sample stacking   全文下載

Determination of quetiapine and its metabolites in plasma by field-enhanced sample stacking

"Quetiapine is an atypical antipsychotic drug that can be used to treat mental disorders, including schizophrenia, bipolardisorder and Alzheimer's disease. Quetiapine is mainly converted into the active metabolites of norquetiapine and7-hydroxyquetiapine by the liver enzymes CYP3A4 and CYP2D6. In this study, liquid-liquid extraction (LLE) was usedas a sample pretreatment method to eliminate interferences in plasma. tert-Butyl methyl ether was chosen as theextraction solvent. Field-enhanced sample injection (FESS), an online preconcentration technique, was used to analyzequetiapine and its metabolites norquetiapine and 7-hydroxyquetiapine in plasma. The optimal separation condition was120 mM phosphate (pH 4.0) containing 0.005% (w/v) polyvinyl pyrrolidone and 40% (v/v) methanol. The methanol plugwas 0.3 psi for 6 s, the sample was electrokinetic injection by 10 kV for 60 s at positive polarity, and the separationvoltage was set at 26 kV. In this experiment, quetiapine, norquetiapine and 7-hydroxyquetiapine were successfullyextracted from plasma by the LLE method and stacking and separated by FESS within 15 min. The limits of detection (S/N¼3) of quetiapine, norquetiapine and 7-hydroxyquetiapine were 0.25 ng/mL, 0.50 ng/mL and 1.00 ng/mL, respectively.The linear ranges of quetiapine, norquetiapine and 7-hydroxyquetiapine were 3e120 ng/mL and the correlation coefficientswere 0.999. Compared with that of the traditional capillary zone electrophoresis method, the sensitivityenrichment of analytes was 463-835-fold. The optimal experimental conditions were successfully applied to the analysisof plasma samples from patients taking quetiapine for the treatment of schizophrenia."