Table1_Fatal cases involving new psychoactive substances and trends in analytical techniques.docx

New psychoactive substances (NPS) are an emerging public health issue and deaths are commonly associated with polydrug abuse. Moreover, the number of new substances available is constantly increasing, causing intoxications in low doses, characteristics that impose to toxicology and forensic laboratories to keep routine methods up to date, with high detectability and constantly acquiring new analytical standards. Likewise, NPS metabolites and respective elimination pathways are usually unknown, making it difficult the detection and confirmation of the drug involved in the fatal case in an analytical routine. A literature search was performed on PubMed, Scopus and Web of Science databases for papers related to chromatographic analyses from fatal cases related to NPS use published from 2016 to 2021. A total of 96 papers were retrieved and reviewed in this study. Opioids, synthetic cathinones, phenethylamines/amphetamines and cannabinoids were the NPS classes most found in the fatal cases. In many cases, multiple compounds were detected in the biological samples, including prescription and other illegal drugs. Liquid chromatography-tandem mass spectrometry, an alternative to overcome the gas chromatography–mass spectrometry limitations for some compounds, was the analytical technique most used in the studies, and high resolution mass spectrometry was often applied to NPS metabolite investigation and structural characterization and identification of unknown compounds. Toxicological screening and quantitation methods need to be continuously updated to include new substances that are emerging on the drug market that can be fatal at very low doses.

新型精神活性物质（NPS）已成为一项日益突出的公共卫生问题，其滥用常与死亡事件相关联。此外，可用的新型物质数量持续增加，低剂量即可引起中毒，这些特性要求毒理学和法医实验室不断更新常规方法，以实现高检测率和持续获取新的分析标准。同样，NPS的代谢物及其相应的排泄途径通常未知，这使得在分析常规中对涉及致命病例的药物进行检测和确认变得十分困难。本研究在PubMed、Scopus和Web of Science数据库中进行了文献检索，以寻找2016年至2021年间关于NPS使用相关致命案件色谱分析的论文。共检索并审查了96篇论文。在致命案件中，最常发现的NPS类别包括阿片类药物、合成卡西酮、苯乙胺/苯丙胺和大麻素。在许多情况下，生物样本中检测到多种化合物，包括处方药和其他非法药物。液相色谱-串联质谱法，作为一种克服某些化合物气相色谱-质谱法局限性的替代方法，是研究中使用最多的分析技术，而高分辨率质谱法常被应用于NPS代谢物的研究以及未知化合物的结构表征和鉴定。为了包括药市场上新兴的、低剂量即可致命的新物质，毒理学筛查和定量方法需要不断更新。