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.

中文翻译：

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使用斑马鱼和人肝微粒体作为LC-QE-HF-MS的生物转化系统快速鉴定MDMB-CHMINACA代谢物。

MDMB-CHMINACA是一种新合成的大麻素，适用于美国NMS Lab。由于目前尚无有关MDMB-CHMINACA代谢的公开数据，我们旨在鉴定其生物转化途径和主要代谢产物。采用全扫描正离子模式的液相色谱Q活性HF混合四极杆轨道质谱（LC-QE-HF-MS）和精确质量测量的靶向MS-MS（ddms2）技术分析了代谢位点和途径。的体内建立斑马鱼的代谢动物模型来验证MDMB-CHMINACA的代谢途径从人肝微粒体试验中获得的体外。结果表明，在斑马鱼动物模型和人肝微粒体模型中产生了29种代谢产物。生物转化主要发生在化合物的环己基甲基尾部，次要反应也发生在叔丁基链上，并且在吲唑环处没有反应进行分析。我们建议将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，以证明在临床和法医病例中摄入MDMB-CHMINACA。此外，这项研究提供了有关MDMB-CHMINACA代谢的初步信息，这些信息将指导分析标准制造商更好地为新近遇到的名牌药物的进一步研究提供合适的参考。