Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Department of Legal and Occupational Medicine, Toxicology and Public Health, University Hospital of Padova, Padova, Italy.
Drug Test Anal. 2019 Sep;11(9):1377-1386. doi: 10.1002/dta.2666. Epub 2019 Jul 18.
Synthetic cannabinoids (SCs) remain one of the largest groups of new psychoactive substances (NPS) on the European drug market. Although the number of new derivatives occurring on the market has dropped in the last two years, newly emerging NPS still represent a challenge for laboratories performing forensic drug analysis in biological matrices. The newly emerged SC 4F-MDMB-BINACA has been reported by several law enforcement agencies in Europe and the USA since November 2018. This work aimed at revealing urinary markers to prove uptake of 4F-MDMB-BINACA and differentiate from the use of structurally similar SCs. Phase-I metabolites detected in human urine specimens were confirmed by phase-I metabolites generated in vitro using a pooled human liver microsomes (pHLM) assay. Seized materials and test-purchased "legal high" products were analyzed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-quadrupole-time-of-flight-mass spectrometry (LC-qToF-MS). Human urine specimens and pHLM assay extracts were measured with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) and confirmed by LC-qToF-MS. In January 2019, the Institute of Legal Medicine in Erlangen (Germany) identified 4F-MDMB-BINACA in three herbal blends. During the same time period, the described SC was identified in a research chemical purchased online. Investigation of phase-I metabolism led to the metabolites M10 (ester hydrolysis) and M11 (ester hydrolysis and dehydrogenation) as reliable urinary markers. Widespread distribution on the German drug market was proven by analysis of urine samples from abstinence control programs and by frequent detection of 4F-MDMB-BINACA in "herbal blends" and "'research chemicals" purchased via the Internet.
合成大麻素（SCs）仍然是欧洲毒品市场上最大的新型精神活性物质（NPS）群体之一。尽管市场上新出现的衍生物数量在过去两年中有所下降，但新出现的 NPS 仍然对从事生物基质法医药物分析的实验室构成挑战。自 2018 年 11 月以来，欧洲和美国的几家执法机构报告了新出现的 SC 4F-MDMB-BINACA。这项工作旨在揭示尿液标志物，以证明摄入 4F-MDMB-BINACA，并将其与结构相似的 SC 区分开来。在人体尿液样本中检测到的 I 期代谢物通过使用混合人肝微粒体（pHLM）测定的体外 I 期代谢物得到证实。气相色谱-质谱联用（GC-MS）和液相色谱-四极杆飞行时间质谱联用（LC-qToF-MS）分析缴获的材料和购买的“合法兴奋剂”产品。采用液相色谱-电喷雾串联质谱（LC-ESI-MS/MS）对人尿标本和 pHLM 测定提取物进行测定，并通过 LC-qToF-MS 进行确认。2019 年 1 月，埃尔兰根法医学研究所（德国）在三种草药混合物中鉴定出 4F-MDMB-BINACA。在同一时期，在网上购买的研究化学品中鉴定出了描述的 SC。对 I 期代谢的研究导致代谢物 M10（酯水解）和 M11（酯水解和脱氢）作为可靠的尿液标志物。通过对禁欲控制计划中的尿液样本进行分析以及通过频繁检测“草药混合物”和通过互联网购买的“研究化学品”中的 4F-MDMB-BINACA，证明了其在德国毒品市场的广泛分布。
