Ishii Ayumu, Sato Kazuki, Kusakabe Kosuke, Kato Noriyuki, Wada Takeshi
Scientific Crime Laboratory, Kanagawa Prefectural Police Headquarters, 155-1 Yamashitacho, Naka-ku, Yokohama-shi, Kanagawa, Japan.
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba, Japan.
J Anal Toxicol. 2023 Feb 21;47(1):59-65. doi: 10.1093/jat/bkac026.
Various synthetic drugs have appeared over the past years across the world, and phenethylamine derivatives are among them; indeed, aromatic fluoro analogs of methamphetamine and amphetamine have been in the illicit drug market since the early 2000s. Although they are currently widely abused across the world, little information is available on their metabolism and toxicology. Recently, we came across an alleged 2-fluoromethamphetamine (2-FMA) drug abuse case. The urine obtained from the alleged abuser was analyzed as part of a criminal investigation. 2-FMA, 2-fluoroamphetamine (2-FAP) and some related compounds were detected by liquid chromatography-tandem mass spectrometry. In forensic science, both an "unchanged" drug and its metabolite(s) need to be detected in urine to verify the illicit drug use. Notably, the detection of 2-FAP, which is a plausible 2-FMA metabolite, is insufficient as evidence of 2-FMA use because 2-FAP is widely available and may be present as such in taken liquids. In this study, we synthesized analytical standards for N-hydroxy 2-FMA (N-OH-2-FMA) and two diastereomers of 2-fluoroephedrine, which are plausible metabolites of 2-FMA. Using these standards, the urine specimen was found to contain N-OH-2FMA and one diastereomer of 2-fluoroephedrine; moreover, the concentrations of these compounds were successfully determined. The results of our study suggest that N-hydroxylation and aliphatic hydroxylation are the characteristic metabolic pathways of 2-FMA compared with that of methamphetamine. This evidence indicates that both N-OH-2-FMA and 2-fluoroephedrine are plausible candidates as analytical targets for drug-use certification in forensic science.
在过去几年中，世界各地出现了各种合成药物，苯乙胺衍生物便是其中之一；事实上，自21世纪初以来，甲基苯丙胺和苯丙胺的芳香族氟类似物就已出现在非法药物市场上。尽管它们目前在全球被广泛滥用，但关于其代谢和毒理学的信息却很少。最近，我们遇到了一起疑似2-氟甲基苯丙胺（2-FMA）药物滥用案件。从疑似滥用者那里获取的尿液作为刑事调查的一部分进行了分析。通过液相色谱-串联质谱法检测到了2-FMA、2-氟苯丙胺（2-FAP）和一些相关化合物。在法医学中，需要在尿液中检测到“未变化”的药物及其代谢物，以核实非法药物的使用情况。值得注意的是，检测到的2-FAP作为2-FMA的一种可能代谢物，不足以作为2-FMA使用的证据，因为2-FAP广泛存在，可能原样存在于摄入的液体中。在本研究中，我们合成了N-羟基2-FMA（N-OH-2-FMA）以及2-氟麻黄碱的两种非对映异构体的分析标准品，它们是2-FMA可能的代谢物。使用这些标准品，发现尿液样本中含有N-OH-2FMA和2-氟麻黄碱的一种非对映异构体；此外，成功测定了这些化合物的浓度。我们的研究结果表明，与甲基苯丙胺相比，N-羟基化和脂肪族羟基化是2-FMA的特征性代谢途径。这一证据表明，N-OH-2-FMA和2-氟麻黄碱都有可能作为法医学中药物使用认证的分析目标。
