"利用人類肝臟細胞微小體及尿液鑑定3, 4-亞甲基雙氧甲基卡西酮和3, 4-亞甲基雙氧-N-乙基卡西酮之代謝物"

Abstract

合成卡西酮是台灣目前最常被檢出的新興濫用藥物，分別於2012以及2016年被列為第三級管制藥品的3,4-亞甲基雙氧甲基卡西酮與3,4-亞甲基雙氧-N-乙基卡西酮為最常見的兩種合成卡西酮衍生物。為了尋找兩種物質在人類檢體中的檢測生物指標，了解這兩種物質的代謝是非常重要。然而目前對於這兩種物質的代謝研究，尤其針對二級代謝物的部分仍很有限。過去的研究指出3,4-亞甲基雙氧甲基卡西酮與3,4-亞甲基雙氧-N-乙基卡西酮分別能透過五種代謝途徑形成七種代謝產物。本研究利用人類肝細胞成分模擬人體代謝反應，並在液相層析質譜儀以及液相層析高解析質譜儀上，藉由碎片圖譜與精確質量鑑定其代謝產物，總共偵測到八種一級代謝產物以及三種二級代謝產物，其中的三種二級代謝產物DHMC-S、DHEC-S、DHEC-G為首次被合成出來。依此結果建立檢測方法分析已知為3,4-亞甲基雙氧甲基卡西酮與3,4-亞甲基雙氧-N-乙基卡西酮使用者尿液檢體中的代謝物組成，發現dihydromethylone與3-hydroxy-4-methoxymeth-cathinone (3-OH-4-MeO-MC-G)及其異構物4-hydroxy-3-methoxymeth-cathinone (4-OH-3-MeO-MC-G)其中之一為3,4-亞甲基雙氧甲基卡西酮使用者尿液中主要代謝物；dihydroethylone與DHEC-S為3,4-亞甲基雙氧-N-乙基卡西酮使用者尿液中主要代謝物，但須有更多尿液樣本讓代謝趨勢更加明確。

Synthetic cathinone is the most frequently abused new psychoactive substances (NPS) in Taiwan. Methylone and ethylone, which were categorized as scheduled III drug in 2012 and 2016 in Taiwan, are two derivatives of synthetic cathinone. It is important to investigate the metabolism of methylone and ethylone in order to find specific markers in human specimen. However, the metabolic profile of these two compounds are still limited especially for phase II metabolites. In previous study, methylone and ethylone each formed 7 metabolites through 5 metabolic pathways. In this study, we in vitro synthesized phase I and phase II metabolites by human liver microsomes and cytosols, and observed metabolites by fragment pattern and accurate mass using liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-high resolution mass spectrometry (LC-HRMS). Total eight phase I metabolites and three phase II metabolites were detected. Three in vitro phase II metabolites, sulfate conjugate of dihydroxymethcathinone (DHMC-S) from methylone, sulfate conjugate of dihydroxyethcathinone (DHEC-S) from ethylone and glucuronide conjugate of dihydroxymethcathinone (DHEC-G) from ethylone have never reported before. The method was established to identify the metabolites in human specimens. Urine samples from methylone and ethylone abusers were analyzed to evaluate the composition of metabolites. Dihydromethylone and glucuronide conjugate of 3-hydroxy-4-methoxymeth-cathinone (3-OH-4-MeO-MC-G) or its isomer 4-OH-3-MeO-MC-G were major metabolites of methylone, and Dihydroethylone and DHEC-S were major metabolites of ethylone in abusers urine samples. But more urine sample should be analyzed to make the metabolic trend more obvious.