Simultaneous Quantification of 38 Psychotropic Drugs and Relevant Metabolites in Blood using LC-MS-MS

Simultaneous Quantification of 38 Psychotropic Drugs and Relevant Metabolites in Blood using LC-MS-MS
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使用 LC-MS-MS 同时定量血液中 38 种精神药物和相关代谢物

DOI:
10.1093/jat/bkaa085
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发表时间:
2021-05-01
影响因子:
2.5
通讯作者:
Jiang,Yan
Jiang,Yan
中科院分区:
医学3区
文献类型:
--
作者:
Zhu,Rongzhe;Dong,Xiaoru;Jiang,Yan

文献摘要

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抗抑郁药和抗精神病药合并处方的趋势正在增加。这需要一种用于法医和临床的准确筛查和量化方法。在本研究中,开发并验证了液相色谱-串联质谱(LC-MS-MS)方法,用于同时测定和定量小体积(200 μL)人全血中的38种抗抑郁药、抗精神病药及其相关代谢物。使用液-液萃取法萃取分析物和氘代内标物。使用配备ACQUITY UPLC® BEH苯基色谱柱的LC-MS-MS系统,在正电喷雾电离模式下进行分析物的分离、测定和定量。经验证,证明该分析方法具有高度灵敏度,检测限范围为0.0005 - 1 ng/mL,定量下限范围为0.002 - 2 ng/mL。所有分析物的偏倚以及运行内和运行间精密度均在14.7%范围内。回收率重复性好,35种分析物的回收率均> 50%。评价稀释度,以确保完全涵盖目标化合物的治疗和毒性血液浓度范围。最后,该方法被应用于真实的全血样本收集的法医案件,这表明其实际效用提供准确和全面的信息,死者以前的药物。
The trend for the concomitant prescription of antidepressants and antipsychotics is increasing. This calls for a veracious screening and quantifying method for forensic and clinical use. In this study, a liquid chromatography–tandem mass spectrometry (LC–MS-MS) method was developed and validated for the simultaneous determination and quantification of 38 antidepressants, antipsychotics and relevant metabolites in small volumes (200 μL) of human whole blood. Analytes and deuterated internal standards were extracted using liquid–liquid extraction. The separation, determination and quantification of the analytes were performed using an LC–MS-MS system equipped with an ACQUITY UPLC® BEH Phenyl Column under a positive electrospray ionization mode. After validation, the analytical procedure was proved to be highly sensitive, with a limit of detection ranging from 0.0005 to 1 ng/mL and a lower limit of quantification ranging from 0.002 to 2 ng/mL. Bias and within- and between-run precision were within 14.7% for all analytes. Recoveries were reproducible and those of 35 analytes were >50%. Dilution integrity was evaluated to ensure that the therapeutic and toxic blood concentration ranges of target compounds were fully covered. Finally, this method was applied to authentic whole blood samples collected from two forensic cases, which demonstrated its practical usefulness of providing accurate and comprehensive information concerning the previous medication of the deceased.