利用尿液中非法海洛因之雜質代謝物確認非法海洛因之使用

Abstract

確認海洛因施用者主要倚靠6-乙醯嗎啡的檢出，僅檢出嗎啡成分不能證明施用海洛因。但由於6-乙醯嗎啡體內半衰期短，限制了6-乙醯嗎啡的應用價值。然而，不同於高純度的全合成海洛因，非法海洛因源產於罌粟中之嗎啡，成品含多種具特異性的乙醯化植物鹼雜質。為輔助確認施用海洛因，我們利用人類肝細胞成分模擬人體代謝反應，於體外合成此類特異性雜質的可能代謝物，依此開發液相層析質譜檢測方法，並分析已知為海洛因使用者的尿液檢體。本研究經由分析精確質量與碎片圖譜找到12個代謝物，其中8個未曾報導過。此外，代謝物ATM4S在真實檢體中驗出，14件6-乙醯嗎啡陽性檢體中檢出9件，7件嗎啡陽性而6-乙醯嗎啡陰性的檢體中檢出2件。暗示ATM4S應與6-乙醯嗎啡有相關性，且體內陽性反應時間可能超過6-乙醯嗎啡。 關鍵字：液相層析串聯質譜分析、高解析質譜分析、法醫毒理學、非法海洛因、代謝物鑑定、乙醯化蒂巴因、罌粟植物鹼、體外代謝反應

In the forensic toxicology, it is a challenge to confirm heroin administration, especially for those who are only be confirmed the presence of morphine but no detectable 6-acetylmorphine in their biological samples. However, illicit heroin, different from pharmaceutical heroin with high purity, is manufactured from the capsules of Papaver somniferum with a plenty of alkaloid impurities. Thebaine, one of the alkaloids, can be acetylated during the manufacturing process, and forming unusual rearrangement products, which have been thought to be specific features of illicit heroin. To apply these impurities as a marker in biological fluid to confirm heroin administration, we in vitro synthesized the phase I and phase II metabolites with human liver subfractions, and established a method using liquid chromatography-mass spectrometry. Urine samples from heroin abuser were analyzed to verify if the metabolites from acetylated thebaines can be detected. There were 12 metabolites identified by accurate masses and fragmentation patterns, and 8 of which have never been reported before. Besides, metabolite – ATM4S was detected in the real urine samples: 9 out of 14 samples presented with 6-acetylmorphine; 2 out of 7 samples only presented with morphine. Keywords: Liquid chromatography-tandem mass spectrometry; high resolution mass spectrometry; forensic toxicology; illicit heroin; metabolite identification; acetylated thebaines; alkaloids of Papaver somniferum; in vitro metabolism