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

Tai-Ling Liu ^a,b,1, Li-Shan Fang ^c,1, Jing-Ru Liou ^d, Jia-Shan Dai ^e, Yen-Ling Chen ^c,e,f,*

a Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

b Department of Psychiatry, School of Medicine and Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

c Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan

d Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

e Department of Chemistry and Biochemistry, National Chung Cheng University, Chia-Yi, Taiwan

f Center for Nano Bio-Detection, National Chung Cheng University, Chia-Yi, Taiwan

Quetiapine is an atypical antipsychotic drug that can be used to treat mental disorders, including schizophrenia, bipolar disorder and Alzheimer's disease. Quetiapine is mainly converted into the active metabolites of norquetiapine and 7-hydroxyquetiapine by the liver enzymes CYP3A4 and CYP2D6. In this study, liquid-liquid extraction (LLE) was used as a sample pretreatment method to eliminate interferences in plasma. tert-Butyl methyl ether was chosen as the extraction solvent. Field-enhanced sample injection (FESS), an online preconcentration technique, was used to analyze quetiapine and its metabolites norquetiapine and 7-hydroxyquetiapine in plasma. The optimal separation condition was 120 mM phosphate (pH 4.0) containing 0.005% (w/v) polyvinyl pyrrolidone and 40% (v/v) methanol. The methanol plug was 0.3 psi for 6 seconds, the sample was electrokinetic injection by 10 kV for 60 seconds at positive polarity, and the separation voltage was set at 26 kV. In this experiment, quetiapine, norquetiapine and 7-hydroxyquetiapine were successfully extracted from plasma by the LLE method and stacking and separated by FESS within 15 min. The limits of detection (S/N=3) 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 3-120 ng/mL and the correlation coefficients were 0.999. Compared with that of the traditional capillary zone electrophoresis method, the sensitivity enrichment of analytes was 463-835-fold. The optimal experimental conditions were successfully applied to the analysis of plasma samples from patients taking quetiapine for the treatment of schizophrenia.

Keywords: Field-enhanced sample stacking, Liquid-liquid extraction, Metabolites, Plasma, Quetiapine

https://doi.org/10.38212/2224-6614.3378