Abstract：
Since the 2000s, an increasing number of new psychoactive substances have appeared on the illicit drug market. β-Keto-arylcyclohexylamine compounds play important pharmacological roles in anesthesia; however, because these new psychoactive substances have rapidly increasing illicit recreational use, the lack of detailed toxicity data are of particular concern. Therefore, analysis of their metabolites can help forensic personnel provide references and suggestions on whether a suspect has taken an illicit new psychoactive β-keto-arylcyclohexylamine. The present study investigated the in vitro and in vivo metabolism and metabolites of three β-keto-arylcyclohexylamines: deschloro-N-ethyl-ketamine, fluoro-N-ethyl-ketamine and bromoketamine. In vitro and in vivo models were established using zebrafish and human liver microsomes for analysis of Phase I and Phase II metabolites by liquid chromatography-high-resolution mass spectrometry. Altogether, 49 metabolites were identified. The results were applied for the subject urine samples of known fluoro-N-ethyl-ketamine consumer screen analysis in forensic cases. Hydroxy-deschloro-N-ethyl-ketamine, hydroxy-fluoro-N-ethyl-ketamine and hydroxy-bromoketamine were recommended as potential biomarkers for documenting intake in clinical and forensic cases.
摘要：
自2000年以来，越来越多的新精神活性物质出现在非法药物市场上。β-酮基芳基环己胺化合物在麻醉中起着重要的药理作用；然而，因为这些新的精神活性物质正在迅速增加非法娱乐用途，缺乏详细的毒性数据尤其令人担忧。因此,对其代谢物的分析可以帮助法医人员对嫌疑人是否服用了非法的新型精神活性β-酮基芳基环己胺提供参考和建议。本研究调查了三种β-酮-芳基环己基胺的体外和体内代谢和代谢产物：去氯-N-乙基-氯胺酮，氟-N-乙基-氯胺酮和溴氯胺酮。使用斑马鱼和人肝微粒体建立体外和体内模型，通过液相色谱-高分辨率质谱法分析I相和II相代谢物。总之,鉴定了49种代谢物。该结果适用于法医病例中已知的氟-N-乙基-氯胺酮消费者筛查分析的受试者尿液样品。羟基-脱氯-N-乙基-氯胺酮，建议将羟基-氟-N-乙基-氯胺酮和羟基-溴氯胺酮作为潜在的生物标志物,用于记录临床和法医病例的摄入量.
