Metabolism of the tryptamine‐derived new psychoactive substances 5‐MeO‐2‐Me‐DALT, 5‐MeO‐2‐Me‐ALCHT, and 5‐MeO‐2‐Me‐DIPT and their detectability in urine studied by GC–MS, LC–MSn, and LC‐HR‐MS/MS,Drug Testing and Analysis

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Metabolism of the tryptamine‐derived new psychoactive substances 5‐MeO‐2‐Me‐DALT, 5‐MeO‐2‐Me‐ALCHT, and 5‐MeO‐2‐Me‐DIPT and their detectability in urine studied by GC–MS, LC–MSn, and LC‐HR‐MS/MS
Drug Testing and Analysis ( IF 2.6 ) Pub Date : 2017-05-10 , DOI: 10.1002/dta.2197
Achim T. Caspar ₁ , Jonas B. Gaab ₁ , Julian A. Michely ₁ , Simon D. Brandt _{2,

3} , Markus R. Meyer ₁ , Hans H. Maurer ₁

Affiliation

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–MSⁿ), 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‐MSⁿ, 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.

中文翻译：

通过GC-MS研究了类胰蛋白酶衍生的新型精神活性物质5‐MeO‐2‐Me‐DALT，5‐MeO‐2‐Me‐ALCHT和5‐MeO‐2‐Me‐DIPT的代谢及其在尿液中的可检测性， LC-MSn和LC-HR-MS / MS

许多N，N-二烷基化的色胺都具有精神活性，并作为新的精神活性物质被使用。这项研究的目的是研究5-甲氧基2-甲基-N，N-二烯丙基三苯丙胺（5-MeO-2-Me-DALT ）在标准尿液筛查方法（SUSA）中的I和II期代谢以及可检测性），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）使用气相色谱-质谱（GC-MS），液相色谱与多级精确质谱（LC-MS ⁿ）和液相色谱-高分辨率串联质谱（LC-HR-MS / MS）。为了进行代谢研究，在以20 mg / kg体重（BW）向雄性Wistar大鼠施用化合物后的24小时内收集了尿液。LC-HR-MS / MS用乙腈沉淀尿液后鉴定出I和II期代谢物。5‐MeO‐2‐Me‐DALT（24期I和12期II期代谢物），5‐MeO‐2‐Me‐ALCHT（24期I和14期II期代谢物）和5‐MeO‐2‐Me‐DIPT （I期20和11期II代谢产物）主要通过O-去甲基化，羟基化，N代谢-去烷基化，以及它们的组合，以及I相代谢产物的葡萄糖醛酸化和硫酸化。与合并的人类肝微粒体和细胞溶质（pHLM和pHLC）的混合物一起温育证实，人类和大鼠的主要代谢反应可能是相同的。此外，最初的CYP活性筛选显示CYP1A2，CYP2C19，CYP2D6和CYP3A4参与羟甲基化，O-去甲基化过程中的CYP2C19和CYP2D6和N-去烷基化过程中的CYP2C19，CYP2D6和CYP3A4 。对于SUSA，GC-MS，LC-MS ⁿ分别以1或0.1 mg / kg BW剂量将LC-HR-MS / MS应用于大鼠尿液样品。与GC-MS SUSA相比，两种LC-MS SUSA都能通过1 mg / kg BW施用后的代谢物检测出5 MeO-2-MeAlCHT和5MeO-2-Me DIPT的摄入量。剂量为0.1 mg / kg体重时使用5-MeO-2-Me-DALT。版权所有©2017 John Wiley＆Sons，Ltd.

更新日期：2017-05-10

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