Forensic-Chemical Division, Bureau of Forensic-Medical Expertise's, Moscow, Russia.
Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, Saint James's Hospital, Dublin, Ireland.
Drug Test Anal. 2019 Sep;11(9):1387-1402. doi: 10.1002/dta.2668. Epub 2019 Jul 10.
Synthetic cannabinoids (SCs), mimicking the psychoactive effects of cannabis, consist of a vast array of structurally diverse compounds. A novel compound belonging to the SC family, (1-(cyclohexylmethyl)-1H-indol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone (named TMCP-CHM in this article) contains a cyclopropane ring that isomerizes during the smoking process, resulting in a ring-opened thermal degradant with a terminal double bond in its structure. Metabolites of TMCP-CHM were tentatively identified in vitro (after incubation of the parent substance with S9 pooled human liver fraction) and in vivo (rat experimental model) studies by accurate-mass liquid chromatography-tandem mass spectrometry (LC-MS/MS). For the identification of the degradant metabolites, and to study biotransformation of parent substance in the human, urine and hair samples from patients, who had ingested the compound and were subsequently admitted to hospital with drug intoxications, were analyzed. Products of mono-, di-, trihydroxylation, carboxylation, and carboxylation combined with hydroxylation of TMCP-CHM and its degradant were detected in human urine. Metabolism of the degradant included addition of water to the terminal double bond followed by dehydration and formation of a cyclic metabolite. Degradant metabolites prevailed in comparison with metabolites of the parent substance in each metabolite group examined, except carboxylation. N-Dealkylated metabolites found in human urine originated only from the degradant. Most of the hydroxy metabolites were detected in human urine in both the free form and as glucuronides. The detection of monohydroxylated (M1.1-M1.3, M/A1.10) and carboxylated/hydroxylated (M4.2, M/A4.3) metabolites of TMCP-CHM and the hydrated form of the monohydroxylated metabolite of the degradant was found to be convenient for routine analysis.
合成大麻素（SCs）模仿大麻的精神活性作用，由结构多样的化合物组成。一种属于 SC 家族的新型化合物，（1-（环己基甲基）-1H-吲哚-3-基）-（2,2,3,3-四甲基环丙基）甲酮（本文中命名为 TMCP-CHM），含有一个环丙烷环，在吸烟过程中发生异构化，导致其结构中具有末端双键的环开热降解产物。TMCP-CHM 的代谢物通过准确质量液相色谱-串联质谱（LC-MS/MS）在体外（在母体物质与 S9 人肝匀浆孵育后）和体内（大鼠实验模型）研究中被初步鉴定。为了鉴定降解代谢物，并研究母体物质在摄入化合物后因药物中毒而住院的患者的人体生物转化，分析了患者的尿液和头发样本。在人尿液中检测到 TMCP-CHM 及其降解产物的单、二、三羟化、羧化以及羧化与羟化产物。降解产物的代谢包括在末端双键上加一分子水，然后脱水形成环状代谢物。降解产物的代谢包括在末端双键上加一分子水，然后脱水形成环状代谢物。降解产物的代谢包括在末端双键上加一分子水，然后脱水形成环状代谢物。与所检查的每个代谢物组中的母体物质代谢物相比，降解产物代谢物占主导地位，除羧化产物外。在人尿液中发现的 N-去烷基代谢物仅来自降解产物。大多数羟基代谢物以游离形式和葡萄糖醛酸形式存在于人尿液中。检测到 TMCP-CHM 的单羟基化（M1.1-M1.3，M/A1.10）和羧基化/羟基化（M4.2，M/A4.3）代谢物以及降解产物的单羟基化代谢物的水合形式，方便进行常规分析。
