The aim of this study was to characterize the in vitro and in vivo metabolism of 2‐aminoindane (2,3‐dihydro‐1H‐inden‐2‐amine, 2‐AI), and N‐methyl‐2‐aminoindane (N‐methyl‐2,3‐dihydro‐1H‐inden‐2‐amine, NM‐2‐AI) after incubations using pooled human liver microsomes (pHLMs), pooled human liver S9 fraction (pS9), and rat urine after oral administration. After analysis using liquid chromatography coupled to high‐resolution mass spectrometry, pHLM incubations revealed that 2‐AI was left unmetabolized, while NM‐2‐AI formed a hydroxylamine and diastereomers of a metabolite formed after hydroxylation in beta position. Incubations using pS9 led to the formation of an acetyl conjugation in the case of 2‐AI and merely a hydroxylamine for NM‐2‐AI. Investigations on rat urine showed that 2‐AI was hydroxylated also forming diasteromers as described for NM‐2‐AI or acetylated similar to incubations using pS9. All hydroxylated metabolites of NM‐2‐AI except the hydroxylamine were found in rat urine as additional sulfates. Assuming similar patterns in humans, urine screening procedures might be focused on the parent compounds but should also include their metabolites. An activity screening using human recombinant N‐acetyl transferase (NAT) isoforms 1 and 2 revealed that 2‐AI was acetylated exclusively by NAT2, which is polymorphically expressed.

中文翻译：

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在体外和体内研究了两种新型精神活性物质（2-氨基茚满和N-甲基-2-氨基茚满）的代谢命运，以支持药物测试。

这项研究的目的是表征2-氨基茚满（2,3-二氢-1 H-茚满-2-胺，2-AI）和N-甲基-2-氨基茚满（N -甲基-2,3-二氢-1 H用口服人肝微粒体（pHLMs），人肝S9级分（pS9）和大鼠尿液孵育后孵育2-茚二胺（NM-2-AI）。使用液相色谱和高分辨率质谱分析后，pHLM孵育显示2-AI未代谢，而NM-2-AI形成羟胺，β位羟基化后形成的代谢产物的非对映异构体。使用pS9进行孵育会在2-AI情况下形成乙酰基共轭反应，而对于NM-2-AI而言仅会生成羟胺。对大鼠尿液的研究表明，2-NM被羟化也形成了非对映异构体（如NM-2-AI所述）或被乙酰化，类似于使用pS9进行孵育。在大鼠尿液中发现了NM-2-AI的所有羟化代谢产物（羟胺除外）为额外的硫酸盐。假设人类的模式相似，尿液筛查程序可能集中在母体化合物上，但也应包括其代谢产物。使用人类重组子进行活性筛选N-乙酰基转移酶（NAT）亚型1和2表明2-AI仅被NAT2乙酰化，而NAT2是多态表达的。