Fabregat-Safont David, Mardal Marie, Sancho Juan V, Hernández Félix, Linnet Kristian, Ibáñez María
Research Institute for Pesticides and Water, University Jaume I, Avda. Sos Baynat s/n, 12071, Castellón, Spain.
Department of Forensic Medicine, Section of Forensic Chemistry, Faculty of Health and Medicinal Sciences, University of Copenhagen, Frederik V's vej 11, 2100, København Ø, Denmark.
J Pharm Anal. 2020 Apr;10(2):147-156. doi: 10.1016/j.jpha.2019.12.006. Epub 2019 Dec 28.
Synthetic cathinones are new psychoactive substances that represent a health risk worldwide. For most of the 130 reported compounds, information about toxicology and/or metabolism is not available, which hampers their detection (and subsequent medical treatment) in intoxication cases. The principles of forensic analytical chemistry and the use of powerful analytical techniques are indispensable for stablishing the most appropriate biomarkers for these substances. Human metabolic fate of synthetic cathinones can be assessed by the analysis of urine and blood obtained from authentic consumers; however, this type of samples is limited and difficult to access. In this work, the metabolic behaviour of three synthetic cathinones (4-CEC, 4-CPrC and 5-PPDi) and one amphetamine (3-FEA) has been evaluated by incubation with pooled human hepatocytes and metabolite identification has been performed by high-resolution mass spectrometry. This approach has previously shown its feasibility for obtaining excretory human metabolites. 4-CEC and 3-FEA were not metabolised, and for 4-CPrC only two minor metabolites were obtained. On the contrary, for the recently reported 5-PPDi, twelve phase I metabolites were elucidated. Up to our knowledge, this is the first metabolic study of an indanyl-cathinone. Data reported in this paper will allow the detection of these synthetic stimulants in intoxication cases, and will facilitate future research on the metabolic behaviour of other indanyl-based cathinones.
合成卡西酮是新型精神活性物质，在全球范围内构成健康风险。对于已报告的130种化合物中的大多数，毒理学和/或代谢方面的信息尚不可得，这阻碍了在中毒病例中对它们的检测（以及后续的医学治疗）。法医分析化学原理和强大分析技术的应用对于确定这些物质最合适的生物标志物必不可少。合成卡西酮在人体中的代谢情况可通过分析从实际使用者那里获取的尿液和血液来评估；然而，这类样本有限且难以获取。在这项研究中，通过与汇集的人肝细胞孵育评估了三种合成卡西酮（4-CEC、4-CPrC和5-PPDi）和一种苯丙胺（3-FEA）的代谢行为，并通过高分辨率质谱法进行了代谢物鉴定。这种方法此前已证明其在获取人体排泄性代谢物方面的可行性。4-CEC和3-FEA未发生代谢，对于4-CPrC仅获得了两种次要代谢物。相反，对于最近报道的5-PPDi，阐明了12种I相代谢物。据我们所知，这是对茚满基卡西酮的首次代谢研究。本文报告的数据将有助于在中毒病例中检测这些合成兴奋剂，并将促进未来对其他茚满基卡西酮代谢行为的研究。
