Chen Xiujuan, Zheng Shuiqing, Le Jian, Qian Zheyuan, Zhang Runsheng, Hong Zhanying, Chai Yifeng
Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, Shanghai Key Laboratory for Pharmaceutical Metabolites Research, Shanghai 200433, China; Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China.
Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, Shanghai Key Laboratory for Pharmaceutical Metabolites Research, Shanghai 200433, China; Shanghai Institute of Forensic Science, Shanghai Key Laboratory of Crime Scene Evidence, Shanghai 200083, China.
J Pharm Biomed Anal. 2017 Aug 5;142:19-27. doi: 10.1016/j.jpba.2017.04.032. Epub 2017 Apr 29.
Antidepressant drugs are widely used in the treatment of different psychiatric disorders, as well as in conjunction with antipsychotics for the treatment of major depressive disorder. In this study, a simple and rapid ultrasound-assisted low-density solvent dispersive liquid-liquid microextraction (UA-LDS-DLLME) method was developed for the simultaneous determination of 12 new antidepressants (norfluoxetine, fluoxetine, fluvoxamine, agomelatine, mirtazapine, moclobemide, melitracen, N-desmethylmirtazapine, maprotiline, sertraline, citalopram, paroxetine) and 2 antipsychotics (clozapine and haloperidol) in human whole blood by gas chromatography-mass spectrometry (GC-MS). Different parameters affecting the UA-LDS-DLLME were optimized and the optimal conditions were as follows: 100μL of toluene as extraction solvent, extraction pH 12 and 3min of ultrasound stirring. Good linearity (R≥0.991) was obtained at the concentration range of 15-1500ng/mL for norfluoxetine, fluoxetine, fluvoxamine, melitracen, maprotiline and citalopram, and 5-500ng/mL for agomelatine, mirtazapine, moclobemide, N-desmethylmirtazapine, sertraline, paroxetine, clozapine and haloperidol. The intra-day and inter-day precision were all less than 10%, and accuracy of intra-day and inter-day were in the range of -12.7% to 7.9% and -13.9 to 11.8%, respectively. The extraction recoveries of most analytes were more than 60%. The UA-LDS-DLLME/GC-MS method was demonstrated with acceptable precision, accuracy and good specificity for the simultaneous determination of 12 antidepressants and 2 antipsychotics, and has been successfully applied in a real case.
抗抑郁药物广泛用于治疗各种精神疾病，也与抗精神病药物联合用于治疗重度抑郁症。在本研究中，开发了一种简单快速的超声辅助低密度溶剂分散液液微萃取（UA-LDS-DLLME）方法，用于通过气相色谱-质谱联用（GC-MS）同时测定人全血中的12种新型抗抑郁药（去甲氟西汀、氟西汀、氟伏沙明、阿戈美拉汀、米氮平、吗氯贝胺、美利曲辛、N-去甲基米氮平、马普替林、舍曲林、西酞普兰、帕罗西汀）和2种抗精神病药（氯氮平和氟哌啶醇）。对影响UA-LDS-DLLME的不同参数进行了优化，最佳条件如下：100μL甲苯作为萃取溶剂，萃取pH值为12，超声搅拌3分钟。去甲氟西汀、氟西汀、氟伏沙明、美利曲辛、马普替林和西酞普兰在15-1500ng/mL浓度范围内线性良好（R≥0.991），阿戈美拉汀、米氮平、吗氯贝胺、N-去甲基米氮平、舍曲林、帕罗西汀、氯氮平和氟哌啶醇在5-500ng/mL浓度范围内线性良好。日内和日间精密度均小于10%，日内和日间准确度分别在-12.7%至7.9%和-13.9%至11.8%范围内。大多数分析物的萃取回收率超过60%。UA-LDS-DLLME/GC-MS方法在同时测定12种抗抑郁药和2种抗精神病药方面具有可接受的精密度、准确度和良好的特异性，并已成功应用于实际案例。
