Key Laboratory of Evidence Science, China University of Political Science and Law, Beijing, 100025, China.
Key laboratory of Sichuan higher education, Criminal Science and Technology Laboratory, Sichuan, 646000, China.
J Anal Toxicol. 2021 Jan 21;44(9):1012-1026. doi: 10.1093/jat/bkaa001.
MDMB-CHMINACA is a newly synthetic cannabinoid, which scoped in NMS Lab, USA. Since there are currently no published data on MDMB-CHMINACA metabolism, we aimed to identify its biotransformation pathways and major metabolites. Liquid chromatography Q-exactive HF hybrid quadrupole-orbitrap mass spectrometry (LC-QE-HF-MS) using full scan positive ion mode and targeted MS-MS (ddms2) techniques with accurate mass measurement were employed to analyze the metabolic sites and pathways. An in vivo metabolic animal model of zebrafish was established to verify the metabolic pathways of MDMB-CHMINACA obtained from human liver microsomal experiment in vitro. The results showed that 29 metabolites were generated in the zebrafish animal model and human liver microsomes model. Biotransformations mainly occurred at the cyclohexylmethyl tail of the compound, minor reactions also occurred at the tert-butyl chain and no reaction was analyzed at the indazole ring. We recommend M1 group (MDMB-CHMINACA ester hydroxylation) and M2 group (MDMB-CHMINACA monohydroxylation) as the potential poisoning markers to document MDMB-CHMINACA intake in clinical and forensic cases. Additionally, this study provides preliminary information regarding the metabolism of MDMB-CHMINACA that will guide analytical standard manufacturers to better provide suitable references for further studies on newly encountered designer drugs.
MDMB-CHMINACA 是一种新合成的大麻素，在美国 NMS 实验室进行了研究。由于目前尚无关于 MDMB-CHMINACA 代谢的已发表数据，我们旨在确定其生物转化途径和主要代谢物。采用液相色谱 Q-Exactive HF 混合四极杆轨道阱质谱（LC-QE-HF-MS），采用全扫描正离子模式和靶向 MS-MS（ddms2）技术，结合精确质量测量，分析代谢部位和途径。建立了斑马鱼体内代谢动物模型，以验证从人肝微粒体实验体外获得的 MDMB-CHMINACA 的代谢途径。结果表明，在斑马鱼动物模型和人肝微粒体模型中生成了 29 种代谢物。生物转化主要发生在化合物的环己基甲基尾部，少量反应也发生在叔丁基链上，而在吲哚环上未分析到反应。我们建议 M1 组（MDMB-CHMINACA 酯羟基化）和 M2 组（MDMB-CHMINACA 单羟基化）作为潜在的中毒标志物，以记录临床和法医案例中 MDMB-CHMINACA 的摄入情况。此外，本研究提供了关于 MDMB-CHMINACA 代谢的初步信息，这将指导分析标准制造商为进一步研究新出现的设计药物提供更合适的参考。
