Caspar Achim T, Gaab Jonas B, Michely Julian A, Brandt Simon D, Meyer Markus R, Maurer Hans H
Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical, Pharmacology and Toxicology, Saarland University, Kirrberger Str. 100, Building 46, D-66421, Homburg (Saar), Germany.
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, James, Parsons Building, Byrom Street, Liverpool, L3 3AF, UK.
Drug Test Anal. 2018 Jan;10(1):184-195. doi: 10.1002/dta.2197. Epub 2017 May 10.
Many N,N-dialkylated tryptamines show psychoactive properties and were encountered as new psychoactive substances. The aims of the presented work were to study the phase I and II metabolism and the detectability in standard urine screening approaches (SUSA) of 5-methoxy-2-methyl-N,N-diallyltryptamine (5-MeO-2-Me-DALT), 5-methoxy-2-methyl-N-allyl-N-cyclohexyltryptamine (5-MeO-2-Me-ALCHT), and 5-methoxy-2-methyl-N,N-diisopropyltryptamine (5-MeO-2-Me-DIPT) using gas chromatography-mass spectrometry (GC-MS), liquid chromatography coupled with multistage accurate mass spectrometry (LC-MS ), and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS). For metabolism studies, urine was collected over a 24 h period after administration of the compounds to male Wistar rats at 20 mg/kg body weight (BW). Phase I and II metabolites were identified after urine precipitation with acetonitrile by LC-HR-MS/MS. 5-MeO-2-Me-DALT (24 phase I and 12 phase II metabolites), 5-MeO-2-Me-ALCHT (24 phase I and 14 phase II metabolites), and 5-MeO-2-Me-DIPT (20 phase I and 11 phase II metabolites) were mainly metabolized by O-demethylation, hydroxylation, N-dealkylation, and combinations of them as well as by glucuronidation and sulfation of phase I metabolites. Incubations with mixtures of pooled human liver microsomes and cytosols (pHLM and pHLC) confirmed that the main metabolic reactions in humans and rats might be identical. Furthermore, initial CYP activity screenings revealed that CYP1A2, CYP2C19, CYP2D6, and CYP3A4 were involved in hydroxylation, CYP2C19 and CYP2D6 in O-demethylation, and CYP2C19, CYP2D6, and CYP3A4 in N-dealkylation. For SUSAs, GC-MS, LC-MS , and LC-HR-MS/MS were applied to rat urine samples after 1 or 0.1 mg/kg BW doses, respectively. In contrast to the GC-MS SUSA, both LC-MS SUSAs were able to detect an intake of 5-MeO-2-Me-ALCHT and 5-MeO-2-Me-DIPT via their metabolites following 1 mg/kg BW administrations and 5-MeO-2-Me-DALT following 0.1 mg/kg BW dosage. Copyright © 2017 John Wiley & Sons, Ltd.
许多N,N - 二烷基化色胺具有精神活性，被视为新型精神活性物质。本研究的目的是使用气相色谱 - 质谱联用仪（GC - MS）、液相色谱 - 多级精确质谱联用仪（LC - MS）和液相色谱 - 高分辨率串联质谱联用仪（LC - HR - MS/MS），研究5 - 甲氧基 - 2 - 甲基 - N,N - 二烯丙基色胺（5 - MeO - 2 - Me - DALT）、5 - 甲氧基 - 2 - 甲基 - N - 烯丙基 - N - 环己基色胺（5 - MeO - 2 - Me - ALCHT）和5 - 甲氧基 - 2 - 甲基 - N,N - 二异丙基色胺（5 - MeO - 2 - Me - DIPT）的I相和II相代谢情况以及在标准尿液筛查方法（SUSA）中的可检测性。对于代谢研究，以20 mg/kg体重（BW）将化合物给予雄性Wistar大鼠后，在24小时内收集尿液。通过LC - HR - MS/MS对用乙腈沉淀尿液后的I相和II相代谢产物进行鉴定。5 - MeO - 2 - Me - DALT（24种I相和12种II相代谢产物）、5 - MeO - 2 - Me - ALCHT（24种I相和14种II相代谢产物）和5 - MeO - 2 - Me - DIPT（20种I相和11种II相代谢产物）主要通过O - 去甲基化、羟基化、N - 去烷基化及其组合进行代谢，以及通过I相代谢产物的葡萄糖醛酸化和硫酸化进行代谢。用人肝微粒体和胞质溶胶混合物（pHLM和pHLC）进行的孵育证实，人和大鼠的主要代谢反应可能相同。此外，初步的CYP活性筛选显示，CYP1A2、CYP2C19、CYP2D6和CYP3A4参与羟基化反应，CYP2C19和CYP2D6参与O - 去甲基化反应，CYP2C19、CYP2D6和CYP3A4参与N - 去烷基化反应。对于SUSA，分别将GC - MS（1 mg/kg BW剂量）、LC - MS和LC - HR - MS/MS（0.1 mg/kg BW剂量）应用于大鼠尿液样本。与GC - MS SUSA不同，两种LC - MS SUSA都能够通过其代谢产物检测到1 mg/kg BW给药后的5 - MeO - 2 - Me - ALCHT和5 - MeO - 2 - Me - DIPT以及0.1 mg/kg BW剂量后的5 - MeO - 2 - Me - DALT的摄入情况。版权所有© 2017 John Wiley & Sons, Ltd.
