Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, Center for Molecular Signaling (PZMS), 66421 Homburg, Germany.
Applied Pharmacy, University of Applied Sciences Kaiserslautern, Campus Pirmasens, 66953 Pirmasens, Germany.
J Anal Toxicol. 2021 Feb 13;45(2):195-202. doi: 10.1093/jat/bkaa060.
Prerequisites for the reliable identification of substances in terms of forensic and clinical toxicology or doping control include knowledge about their metabolism and their excretion patterns in urine. N-Ethyl-N-propyltryptamine (N-ethyl-N-[2-(1H-indol-3-yl)ethyl]propan-1-amine, EPT) is an N,N-dialkylated tryptamine derivative, sold as new psychoactive substance, and supposed to act as a partial agonist at the 5-HT2A receptor. The aims of the presented study were to elucidate in vitro metabolites of EPT after incubations with pooled human liver S9 fraction (pS9) and in vivo metabolites excreted into rat urine. Finally, suitable analytical target compounds should be identified. Analysis of pS9 incubations using liquid chromatography-high-resolution tandem mass spectrometry revealed EPT metabolites formed after N-dealkylation as well as alkyl and aryl hydroxylation and formation of a hydroxy sulfate. Investigations using rat urine after oral dosing showed that the metabolic pathways of EPT shifted from in vitro hydroxylation of the alkyl amine group to an increased in vivo hydroxylation of the indole ring with several N-dealkyl metabolites. A glucuronic acid conjugate after hydroxylation of the indole ring was additionally found in vivo. The parent compound could not be detected in the rat urine samples. Therefore, analytical methods using mass spectrometry should include hydroxy-EPT and two hydroxy-EPT glucuronide isomers for reliable identification.
对于法医毒理学和临床毒理学或兴奋剂控制中物质的可靠鉴定，先决条件包括了解其代谢以及在尿液中的排泄模式。N-乙基-N-丙基色胺（N-乙基-N-[2-（1H-吲哚-3-基）乙基]丙-1-胺，EPT）是一种 N，N-二烷基色胺衍生物，作为新型精神活性物质出售，被认为是 5-HT2A 受体的部分激动剂。本研究的目的是阐明与混合人肝 S9 级分（pS9）孵育后的 EPT 体外代谢物和在大鼠尿液中排泄的体内代谢物。最后，应确定合适的分析目标化合物。使用液质联用高分辨串联质谱分析 pS9 孵育物显示，EPT 代谢物形成于 N-脱烷基化以及烷基和芳基羟化和形成羟基硫酸盐之后。口服给予大鼠尿液后的研究表明，EPT 的代谢途径从体外烷基胺基团的羟化转变为体内吲哚环的羟化增加，并有几个 N-脱烷基代谢物。还在体内发现了吲哚环羟化后的葡萄糖醛酸缀合物。在大鼠尿液样本中未检测到母体化合物。因此，使用质谱的分析方法应包括羟基-EPT 和两种羟基-EPT 葡萄糖醛酸苷异构体，以进行可靠的鉴定。
