Tang Yiling, Xu Linhao, Guo Zhenshuo, Zhao Junbo, Xiao Yue, Xiang Ping, Xu Lili, Yan Hui
Department of Forensic Toxicology, Shanghai Key Laboratory of Forensic Medicine, Academy of Forensic Science, Shanghai, 200063, China.
Department of Pharmaceutical Analysis, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
Arch Toxicol. 2025 Mar 10. doi: 10.1007/s00204-025-04010-6.
New psychoactive substances (NPS) are substances that are not controlled by international drug control conventions but are abused and pose a threat to public health. Proscaline and methallylescaline are two phenylethylamines with psychoactive and stimulant effects and are also derivatives of the classic hallucinogen mescaline. However, limited toxicity information on proscaline and methallylescaline has hindered the identification of these two NPS. Therefore, data on the metabolic profiles of proscaline and methallylescaline are urgently needed. In this study, high-resolution mass spectrometry was used to establish three complementary metabolism models-computational prediction (in silico), zebrafish (in vivo), and human liver microsomes (in vitro)-to study the in vivo and in vitro metabolic fates of proscaline and methallylescaline. The models provided the first identification of 7 proscaline metabolites and 11 methallylescaline metabolites. In addition, hydroxylated and N-acetylated products were identified as the major metabolites of these two phenylethylamines. This enabled the selection of hydroxylated and N-acetylated metabolites as biomarkers of proscaline and methallylescaline, thereby facilitating the specific detection of the intake of these two NPSs in a relatively wide detection window.
新型精神活性物质（NPS）是不受国际药物管制公约管制但被滥用并对公众健康构成威胁的物质。普罗司卡林和甲基烯丙基麦司卡林是两种具有精神活性和刺激作用的苯乙胺，也是经典致幻剂麦司卡林的衍生物。然而，关于普罗司卡林和甲基烯丙基麦司卡林的毒性信息有限，这阻碍了对这两种新型精神活性物质的识别。因此，迫切需要有关普罗司卡林和甲基烯丙基麦司卡林代谢谱的数据。在本研究中，使用高分辨率质谱建立了三种互补的代谢模型——计算预测（计算机模拟）、斑马鱼（体内）和人肝微粒体（体外）——以研究普罗司卡林和甲基烯丙基麦司卡林在体内和体外的代谢归宿。这些模型首次鉴定出7种普罗司卡林代谢物和11种甲基烯丙基麦司卡林代谢物。此外，羟基化和N-乙酰化产物被鉴定为这两种苯乙胺的主要代谢物。这使得能够选择羟基化和N-乙酰化代谢物作为普罗司卡林和甲基烯丙基麦司卡林的生物标志物，从而在相对较宽的检测窗口内促进对这两种新型精神活性物质摄入情况的特异性检测。
