College of Medicine and Forensics, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Department of Forensic Toxicology, Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Science Platform, Academy of Forensic Science, Shanghai, China.
Drug Test Anal. 2022 Jul;14(7):1300-1309. doi: 10.1002/dta.3255. Epub 2022 Mar 29.
4-Acetoxy-N,N-dimethyltryptamine (4-AcO-DMT, psilacetin, O-acetylpsilocin) is a synthetic tryptamine with psychedelic properties. Psilacetin may also act as precursor drug of psilocin, similar to psilocybin, but little is known about its metabolism. In this study, the phase I and phase II in vitro metabolism of 4-AcO-DMT was investigated with pooled human liver microsomes, and the reaction mixture was analyzed using liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry. Fifteen metabolites were formed after incubation of pooled human liver microsomes with 4-AcO-DMT (12 phase I metabolites and 3 phase II metabolites). The proposed metabolite structures were based on accurate mass analysis and MS/MS fragmentation patterns. The biotransformations included hydrolysis, hydroxylation, N-demethylation, oxidation, and conjugation with glucuronic acid. The hydrolysis metabolite was the most abundant compound. For the development of new methods for the identification of 4-AcO-DMT consumption, the beta-hydroxylation metabolite of 4-AcO-DMT (M2-1) is recommended as a biomarker. The data reported in this work might be applicable to metabolic transformation of 4-AcO-DMT in vivo and also forensically helpful.
4-乙酰氧基-N,N-二甲基色胺（4-AcO-DMT，psilacetin，O-乙酰基 psilocin）是一种具有迷幻特性的合成色胺。Psilacetin 也可能像 psilocybin 一样作为 psilocin 的前体药物，但对其代谢知之甚少。在这项研究中，使用人肝微粒体进行了 4-AcO-DMT 的 I 相和 II 相体外代谢研究，并使用液相色谱-四极杆/静电场轨道阱质谱对反应混合物进行了分析。在与人肝微粒体孵育后，形成了 15 种代谢物（12 种 I 相代谢物和 3 种 II 相代谢物）。基于精确质量分析和 MS/MS 碎片模式提出了代谢物结构。生物转化包括水解、羟化、N-去甲基化、氧化和与葡萄糖醛酸结合。水解代谢物是最丰富的化合物。为了开发鉴定 4-AcO-DMT 消耗的新方法，建议将 4-AcO-DMT 的β-羟化代谢物（M2-1）作为生物标志物。本工作中报道的数据可能适用于 4-AcO-DMT 在体内的代谢转化，也可能对法医学有帮助。
