Tang Yiling, Xu Linhao, Zhao Junbo, Xiang Ping, Yan Hui
Department of Forensic Toxicology, Academy of Forensic Science, Shanghai Key Laboratory of Forensic Medicine, Shanghai 200063, China; Department of Pharmaceutical Analysis, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Department of Forensic Toxicology, Academy of Forensic Science, Shanghai Key Laboratory of Forensic Medicine, Shanghai 200063, China.
J Pharm Biomed Anal. 2023 Nov 30;236:115710. doi: 10.1016/j.jpba.2023.115710. Epub 2023 Sep 6.
The consumption of novel psychoactive substances (NPS) is exceedingly prevalent in society, as these substances are sold and distributed as "legal highs." One novel synthetic cathinone emerging in the market is 1-(1,3-benzodioxol-5-yl)-2-(dimethylamino) pentan-1-one (dipentylone). The goal of this work was to study the in vivo and in vitro metabolism of dipentylone in zebrafish and human liver microsomes (HLMs) by liquid chromatography-high resolution mass spectrometry (LC-HRMS). The zebrafish and HLM samples contained 14 dipentylone metabolites, specifically 12 phase Ⅰ metabolites and 2 phase Ⅱ metabolites. The main metabolic pathways included monohydroxylation (M1 and M2), N-dealkylation (M3), hydroxylation of the aromatic ring and dealkoxylation of M3 (M4), O-dealkylation (M5), N-dealkylation of M5 (M6), reduction of carboxide (M7), monohydroxylation of M5 (M8), dehydrogenation (M9), dealkoxylation (M10), N-dealkylation of M10 (M11), dealkoxylation of M9 (M12), glucuronidation of M5 (M13), and sulfation (M14). The monohydroxylated metabolite (M2) can be recommended as metabolic markers for dipentylone. This study is the first to identify a target compound for monitoring the abuse of dipentylone and to determine the essential chemical structure of the metabolites for further toxicological research.
新型精神活性物质（NPS）在社会中的消费极为普遍，因为这些物质作为“合法兴奋剂”进行销售和分销。市场上出现的一种新型合成卡西酮是1-(1,3-苯并二氧杂环戊烯-5-基)-2-(二甲基氨基)戊烷-1-酮（二苯戊酮）。这项工作的目的是通过液相色谱-高分辨率质谱（LC-HRMS）研究二苯戊酮在斑马鱼和人肝微粒体（HLM）中的体内和体外代谢。斑马鱼和HLM样品中含有14种二苯戊酮代谢物，具体为12种Ⅰ相代谢物和2种Ⅱ相代谢物。主要代谢途径包括单羟基化（M1和M2）、N-脱烷基化（M3）、芳环羟基化和M3的脱烷氧基化（M4）、O-脱烷基化（M5）、M5的N-脱烷基化（M6）、羧化物还原（M7）、M5的单羟基化（M8）、脱氢（M9）、脱烷氧基化（M10）、M10的N-脱烷基化（M11）、M9的脱烷氧基化（M12）、M5的葡萄糖醛酸化（M13）和硫酸化（M14）。单羟基化代谢物（M2）可推荐作为二苯戊酮的代谢标志物。本研究首次确定了监测二苯戊酮滥用的目标化合物，并确定了代谢物的基本化学结构，以供进一步的毒理学研究。
