"以人類肝臟細胞微小體及細胞質體建立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

合成卡西酮為台灣目前最常被檢出的新興濫用物質，而3,4-亞甲基雙氧甲基卡西酮及3,4-亞甲基雙氧-N-乙基卡西酮為常見的其中二種。由於這二種物質的研究在各領域如臨床，藥理，法醫等領域皆相當缺乏，限制了治療與檢測上的發展。過去的文獻指出3,4-亞甲基雙氧甲基卡西酮及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，並利用精確質量與碎片模式，分別在3,4-亞甲基雙氧甲基卡西酮及3,4-亞甲基雙氧-N-乙基卡西酮偵測到其中五種來自於一期代謝路徑的產物，其中二種為共同產物；此外，其中一共同產物3,4-亞甲基雙氧去甲麻黃鹼，首次在液相層析質譜被偵測到。而二期代謝物的部分皆沒有被偵測到。在時序研究的探討中發現，羥基化之代謝產物和共同代謝產物3,4-亞甲基雙氧去甲麻黃鹼，前者於四十八小時後會無法被偵測到，後者則在十二小時後有轉換率上升的現象，有能夠成為評估個體是否有近期使用3,4-亞甲基雙氧甲基卡西酮或3,4-亞甲基雙氧-N-乙基卡西酮之潛力，但須有更多研究以證實其實用性。

Synthetic cathinones are the most prevalent new psychoactive substances (NPS) in Taiwan. Methylone and ethylone are two of them. Since the research in clinical and forensic field are lacking, the development of treatment, detection and investigation are restricted. In the literature review, methylone and ethylone each formed 7 metabolites through 5 metabolic pathways. In this study, the phase I and phase II metabolites of methylone and ethylone were synthesized in vitro by human liver microsome and cyotosol. We utilized the accurate masses and fragmentation patterns to observe the metabolites. Total 8 metabolites were confirmed as previously suspected, with 6 unique and 2 common metabolites. In addition, one of the common metabolite 3’,4’-methylenedioxy-cathine was the first time detected in LC-MS. The phase II metabolites were not detected. In the discussion of time course experiments, the hydroxylated metabolites and 3’,4’-methylenedioxycathine, which the former could not be detected after 48 hours of phase I reaction and the later revealed increased metabolic rate after 12 hours. Therefore, these 2 metabolites may become potential markers that can indicate recent abuse of methylone and ethylone. But further researches should be conducted to prove the hypothesis.