Abstract：
The types and quantities of new psychoactive substances synthesized based on structural modifications have increased rapidly in recent years and pose a great challenge to clinical and forensic laboratories. N-benzyl derivatives of phenethylamines, 25B-NBOH, 25E-NBOH, 25H-NBOH, and 25iP-NBOMe have begun to flow into the black market and have caused several poisoning cases and even fatal cases. The aim of this study was to avoid false negative results by detecting the parent drug and its metabolites to extend the detection window in biological matrices and provide basic data for the simultaneous determination of illegal drugs and metabolites in forensic and emergency cases. To facilitate the comparison of metabolic characteristics, we divided the four compounds into two groups of types, 25X-NBOH and 25X-NBOMe. The in vitro phase I and phase II metabolism of these four compounds was investigated by incubating 10 mg mL-1 pooled human liver microsomes with co-substrates for 180 min at 37 ℃, and then analyzing the reaction mixture using ultrahigh-performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry. In total, 70 metabolites were obtained for the four compounds. The major biotransformations were O-demethylation, hydroxylation, dehydrogenation, N-dehydroxybenzyl, N-demethoxybenzyl, oxidate transformation to ketone and carboxylate, glucuronidation, and their combination reactions. We recommended the major metabolites with high peak area ratio as biomarkers, B2-1 (56.61%), B2-2 (17.43%) and B6 (17.78%) for 25B-NBOH, E2-1 (42.81%), E2-2 (34.90%) and E8-2 (10.18%) for 25E-NBOH, H5 (49.28%), H2-1 (21.54%), and H1 (18.37%) for 25H-NBOH, P3-1 (10.94%), P3-2 (33.18%), P3-3 (14.85%) and P12-2 (23.00%) for 25iP-NBOMe. This is a study to evaluate their metabolic characteristics in detail. Comparative analysis of the N-benzyl derivatives of phenethylamines provided basic data for elucidating their pharmacology and toxicity. Timely analysis of the metabolic profiles of compounds with abuse potential will facilitate the early development of regulatory measures.
摘要：
近年来，基于结构修饰合成的新精神活性物质的类型和数量迅速增加，对临床和法医实验室构成了巨大挑战。苯乙胺的N-苄基衍生物，25B-NBOH,25E-NBOH，25H-NBOH,和25iP-NBOMe已经开始流入黑市，并造成了几起中毒事件，甚至致命的案件。本研究旨在通过检测母体药物及其代谢产物来扩大生物基质中的检测窗口，避免假阴性结果，为法医和急诊案件中非法药物和代谢产物的同时测定提供基础数据。为了便于比较代谢特征，我们把这四种化合物分成两类,25X-NBOH和25X-NBOMe。通过将10mgmL-1的合并人肝微粒体与共底物在37℃下孵育180分钟，研究了这四种化合物的体外I期和II期代谢。然后使用超高效液相色谱-四极杆/静电fi场轨道阱质谱分析反应混合物。总的来说,获得了四个化合物的70个代谢物。主要的生物转化是O-去甲基化，羟基化,脱氢,N-去羟基苄基,N-去甲氧基苄基,氧化转化为酮和羧酸盐，葡糖醛酸化，以及它们的组合反应。我们推荐具有高峰面积比的主要代谢物作为生物标志物，B2-1（56.61%），25B-NBOH的B2-2（17.43％）和B6（17.78％），E2-1（42.81%），25E-NBOH的E2-2（34.90%）和E8-2（10.18%），H5（49.28%），H2-1（21.54%），25H-NBH的H1（18.37%），P3-1（10.94%），P3-2（33.18%），25iP-NBOMe的P3-3（14.85%）和P12-2（23.00%）。这是一项详细评估其代谢特征的研究。苯乙胺的N-苄基衍生物的比较分析为阐明其药理学和毒性提供了基础数据。及时分析具有滥用潜力的化合物的代谢概况将有助于早期制定监管措施。
