Nielsen Kirstine L, Telving Rasmus, Andreasen Mette F, Hasselstrøm Jørgen B, Johannsen Mogens
Department of Forensic Medicine, Section for Forensic Chemistry, Aarhus University , Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus N, Denmark.
J Proteome Res. 2016 Feb 5;15(2):619-27. doi: 10.1021/acs.jproteome.5b01023. Epub 2016 Jan 8.
The illicit drug 3,4-methylenedioxymethamphetamine (MDMA) has profound physiological cerebral, cardiac, and hepatic effects that are reflected in the blood. Screening of blood for MDMA and other narcotics are routinely performed in forensics analysis using ultra-performance liquid chromatography with high-resolution time-of-flight mass spectrometry (UPLC-HR-TOFMS). The aim of this study was to investigate whether such UPLC-HR-TOFMS data collected over a two-year period could be used for untargeted metabolomics to determine MDMA metabolites as well as endogenous changes related to drug response and toxicology. Whole blood samples from living Danish drivers' positive for MDMA in different concentrations were compared to negative control samples using various statistical methods. The untargeted identification of known MDMA metabolites was used to validate the methods. The results further revealed changes of several acylcarnitines, adenosine monophosphate, adenosine, inosine, thiomorpholine 3-carboxylate, tryptophan, S-adenosyl-l-homocysteine (SAH), and lysophospatidylcholine (lysoPC) species in response to MDMA. These endogenous metabolites could be implicated in an increased energy demand and mechanisms related to the serotonergic syndrome as well as drug induced neurotoxicity. The findings showed that it was possible to extract meaningful results from retrospective UPLC-HR-TOFMS screening data for metabolic profiling in relation to drug metabolism, endogenous physiological effects, and toxicology.
非法药物3,4-亚甲基二氧甲基苯丙胺（摇头丸）对大脑、心脏和肝脏有深刻的生理影响，这些影响会在血液中体现出来。在法医分析中，通常使用超高效液相色谱与高分辨率飞行时间质谱联用技术（UPLC-HR-TOFMS）对血液中的摇头丸和其他麻醉药品进行筛查。本研究的目的是调查在两年时间内收集的此类UPLC-HR-TOFMS数据是否可用于非靶向代谢组学，以确定摇头丸代谢物以及与药物反应和毒理学相关的内源性变化。使用各种统计方法，将不同浓度摇头丸检测呈阳性的丹麦在世驾驶员的全血样本与阴性对照样本进行比较。通过对已知摇头丸代谢物的非靶向鉴定来验证方法。结果进一步揭示了几种酰基肉碱、单磷酸腺苷、腺苷、肌苷、硫代吗啉3-羧酸盐、色氨酸、S-腺苷-L-高半胱氨酸（SAH）和溶血磷脂酰胆碱（lysoPC）种类在接触摇头丸后的变化。这些内源性代谢物可能与能量需求增加、与血清素综合征相关的机制以及药物诱导的神经毒性有关。研究结果表明，从回顾性UPLC-HR-TOFMS筛查数据中提取与药物代谢、内源性生理效应和毒理学相关的有意义的代谢谱分析结果是可能的。
