Truta Liliana, Castro André L, Tarelho Sónia, Costa Pedro, Sales M Goreti F, Teixeira Helena M
Forensic Chemistry and Toxicology Service-National Institute of Legal Medicine and Forensic Sciences, Portugal; BioMark, Sensor Research/ISEP, Superior Institute of Engineering of Porto, Portugal.
Forensic Chemistry and Toxicology Service-National Institute of Legal Medicine and Forensic Sciences, Portugal.
J Pharm Biomed Anal. 2016 Sep 5;128:496-503. doi: 10.1016/j.jpba.2016.06.027. Epub 2016 Jun 23.
Depression is among the most prevalent psychiatric disorders of our society, leading to an increase in antidepressant drug consumption that needs to be accurately determined in whole blood samples in Forensic Toxicology Laboratories. For this purpose, this work presents a new gas chromatography tandem mass spectrometry (GC-MS/MS) method targeting the simultaneous and rapid determination of 14 common Antidepressants in whole blood: 13 Antidepressants (amitriptyline, citalopram, clomipramine, dothiepin, fluoxetine, imipramine, mianserin, mirtazapine, nortryptiline, paroxetine, sertraline, trimipramine and venlafaxine) and 1 Metabolite (N-desmethylclomipramine). Solid-phase extraction was used prior to chromatographic separation. Chromatographic and MS/MS parameters were selected to improve sensitivity, peak resolution and unequivocal identification of the eluted analyte. The detection was performed on a triple quadrupole tandem MS in selected ion monitoring (SIM) mode in tandem, using electronic impact ionization. Clomipramine-D3 and trimipramine-D3 were used as deutered internal standards. The validation parameters included linearity, limits of detection, lower limit of quantification, selectivity/specificity, extraction efficiency, carry-over, precision and robustness, and followed internationally accepted guidelines. Limits of quantification and detection were lower than therapeutic and sub-therapeutic concentration ranges. Overall, the method offered good selectivity, robustness and quick response (<16min) for typical concentration ranges, both for therapeutic and lethal levels.
抑郁症是当今社会最普遍的精神疾病之一，这导致抗抑郁药物的消费量增加，法医毒理学实验室需要在全血样本中准确测定其含量。为此，本研究提出了一种新的气相色谱串联质谱法（GC-MS/MS），用于同时快速测定全血中的14种常见抗抑郁药：13种抗抑郁药（阿米替林、西酞普兰、氯米帕明、多塞平、氟西汀、丙咪嗪、米安色林、米氮平、去甲替林、帕罗西汀、舍曲林、曲米帕明和文拉法辛）和1种代谢物（N-去甲基氯米帕明）。在色谱分离之前使用固相萃取。选择色谱和MS/MS参数以提高灵敏度、峰分辨率和对洗脱分析物的明确鉴定。采用电子轰击电离，在串联质谱的选择离子监测（SIM）模式下，使用三重四极杆串联质谱进行检测。氯米帕明-D3和曲米帕明-D3用作氘代内标。验证参数包括线性、检测限、定量下限、选择性/特异性、提取效率、残留、精密度和稳健性，并遵循国际认可的指南。定量限和检测限低于治疗浓度范围和亚治疗浓度范围。总体而言, 该方法对于治疗浓度和致死浓度的典型浓度范围均具有良好的选择性、稳健性和快速响应（<16分钟）。
