Malaca Sara, Bottinelli Charline, Fanton Laurent, Cartiser Nathalie, Carlier Jeremy, Busardò Francesco Paolo
Unit of Forensic Toxicology, Section of Legal Medicine, Department of Biomedical Sciences and Public Health, Marche Polytechnic University, Via Tronto 10/a, 60126 Ancona, Italy.
LAT LUMTOX Laboratory, 32 Rue du 35ème Régiment d'Aviation, 69500 Bron, France.
Metabolites. 2023 Jan 6;13(1):92. doi: 10.3390/metabo13010092.
α-MT is a hallucinogenic and stimulant tryptamine that was involved in several overdose fatalities in the United States and Europe. Analytical toxicology, and particularly the identification of metabolite biomarkers in biological samples, often is the only way to prove tryptamine use in clinical and forensic caseworks. We aimed to identify optimal α-MT metabolite biomarkers of consumption in humans. We identified α-MT metabolites in 10-donor-pooled human hepatocyte incubations and postmortem urine and blood from an α-MT overdose case using in silico metabolite predictions, liquid chromatography high-resolution-tandem mass spectrometry (LC-HRMS/MS), and software-assisted data mining. Nine metabolites were identified in vitro and eight additional metabolites were found in urine; five metabolites were found in blood. Metabolic transformations were hydroxylation, -sulfation, -glucuronidation, -glucuronidation, and -acetylation, consistent with the metabolism of structural analogues. The findings in hepatocyte incubations and postmortem samples were consistent, proving the in vitro model suitability. We suggest α-MT, hydroxy-α-MT glucuronide, and two hydroxy-α-MT sulfates as biomarkers of α-MT use in non-hydrolyzed urine; we suggest α-MT, two hydroxy-α-MT sulfates and -acetyl-α-MT as biomarkers of α-MT use in blood. Further studies on α-MT clinical and forensic caseworks with different doses and routes of administration are necessary to better explore α-MT metabolism.
α-甲基色胺是一种致幻和刺激性色胺，在美国和欧洲涉及多起过量致死案例。分析毒理学，尤其是生物样本中代谢物生物标志物的鉴定，往往是在临床和法医案件工作中证明色胺使用情况的唯一途径。我们旨在确定人体中α-甲基色胺消费的最佳代谢物生物标志物。我们使用计算机代谢物预测、液相色谱高分辨率串联质谱（LC-HRMS/MS）和软件辅助数据挖掘，在10名供体混合的人肝细胞培养物以及一例α-甲基色胺过量案例的死后尿液和血液中鉴定了α-甲基色胺代谢物。在体外鉴定出9种代谢物，在尿液中又发现了8种代谢物；在血液中发现了5种代谢物。代谢转化包括羟基化、硫酸化、葡萄糖醛酸化、葡萄糖醛酸化和乙酰化，与结构类似物的代谢一致。肝细胞培养物和死后样本中的发现一致，证明了体外模型的适用性。我们建议将α-甲基色胺、羟基-α-甲基色胺葡萄糖醛酸苷和两种羟基-α-甲基色胺硫酸盐作为未水解尿液中α-甲基色胺使用的生物标志物；我们建议将α-甲基色胺、两种羟基-α-甲基色胺硫酸盐和乙酰-α-甲基色胺作为血液中α-甲基色胺使用的生物标志物。有必要对不同剂量和给药途径的α-甲基色胺临床和法医案件进行进一步研究，以更好地探索α-甲基色胺的代谢情况。
