Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Department of Psychiatry, School of Medicine and Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
J Food Drug Anal. 2021 Dec 15;29(4):709-716. doi: 10.38212/2224-6614.3378.
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 s, the sample was electrokinetic injection by 10 kV for 60 s 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.
喹硫平是一种非典型抗精神病药物，可用于治疗精神障碍，包括精神分裂症、双相情感障碍和阿尔茨海默病。喹硫平主要通过肝酶 CYP3A4 和 CYP2D6 转化为活性代谢物去甲喹硫平和 7-羟基喹硫平。在本研究中，液液萃取（LLE）被用作样品预处理方法，以消除血浆中的干扰。叔丁基甲基醚被选为萃取溶剂。场增强样品进样（FESS），一种在线浓缩技术，用于分析血浆中的喹硫平和其代谢物去甲喹硫平和 7-羟基喹硫平。最佳分离条件为 120mM 磷酸盐（pH4.0），含有 0.005%（w/v）聚乙烯吡咯烷酮和 40%（v/v）甲醇。甲醇塞为 0.3psi 持续 6s，样品在正极性下以 10kV 进行电动进样 60s，分离电压设置为 26kV。在本实验中，LLE 法成功地从血浆中提取了喹硫平、去甲喹硫平和 7-羟基喹硫平，FESS 进行堆积和分离，在 15min 内完成。喹硫平、去甲喹硫平和 7-羟基喹硫平的检测限（S/N=3）分别为 0.25ng/mL、0.50ng/mL 和 1.00ng/mL。喹硫平、去甲喹硫平和 7-羟基喹硫平的线性范围均为 3-120ng/mL，相关系数均为 0.999。与传统的毛细管区带电泳法相比，分析物的灵敏度富集了 463-835 倍。优化后的实验条件成功应用于服用喹硫平治疗精神分裂症患者的血浆样品分析。
