Wagmann Lea, Schmitt Jana H, Gampfer Tanja M, Brandt Simon D, Scott Kenneth, Kavanagh Pierce V, Meyer Markus R
Department of Experimental and Clinical Toxicology and Pharmacology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, 66421 Homburg, Germany.
The Alexander Shulgin Research Institute, 1483 Shulgin Road, Lafayette, CA 94549, USA.
Metabolites. 2025 Jul 23;15(8):497. doi: 10.3390/metabo15080497.
: The emergence of cathinone-based psychostimulants necessitates ongoing research and analysis of the characteristics and properties of novel derivatives. The metabolic fate of five novel cathinone-derived substances (ASProp, MASProp, MASPent, PySProp, and PySPent) containing a selenophene moiety was investigated in vitro and in vivo. : All compounds were incubated individually with pooled human liver S9 fraction. A monooxygenase activity screening investigating the metabolic contribution of eleven recombinant phase I isoenzymes was conducted. Rat urine after oral administration was prepared by urine precipitation. Liquid chromatography-high-resolution tandem mass spectrometry was used for the analysis of all samples. Reversed-phase liquid chromatography (RPLC) and zwitterionic hydrophilic interaction liquid chromatography (HILIC) were used to evaluate and compare the metabolites' chromatographic resolution. : Phase I reactions of ASProp, MASProp, MASPent, PySProp, and PySPent included -dealkylation, hydroxylation, reduction, and combinations thereof. The monooxygenase activity screening revealed the contribution of various isozymes. Phase II reactions detected in vivo included -acetylation and glucuronidation. Both chromatographic columns complemented each other. : All substances revealed metabolic reactions comparable to those observed for other synthetic cathinones. Contributions from isozymes to their metabolism minimized the risk of drug-drug interactions. The identified metabolites should be considered as targets in human biosamples, especially in urine screening procedures. RPLC and HILIC can both be recommended for this purpose.
卡西酮类精神兴奋剂的出现使得对新型衍生物的特性和性质进行持续研究和分析成为必要。研究了五种含硒吩部分的新型卡西酮衍生物质（ASProp、MASProp、MASPent、PySProp和PySPent）在体外和体内的代谢命运。所有化合物分别与混合的人肝脏S9组分孵育。进行了一项单加氧酶活性筛选，研究了11种重组I相同工酶的代谢贡献。口服给药后的大鼠尿液通过尿液沉淀制备。液相色谱-高分辨率串联质谱用于分析所有样品。反相液相色谱（RPLC）和两性离子亲水相互作用液相色谱（HILIC）用于评估和比较代谢物的色谱分辨率。ASProp、MASProp、MASPent、PySProp和PySPent的I相反应包括脱烷基化、羟基化、还原及其组合。单加氧酶活性筛选揭示了各种同工酶的贡献。体内检测到的II相反应包括乙酰化和葡萄糖醛酸化。两种色谱柱相互补充。所有物质都显示出与其他合成卡西酮观察到的代谢反应相当。同工酶对其代谢的贡献降低了药物相互作用的风险。鉴定出的代谢物应被视为人类生物样品中的靶点，尤其是在尿液筛查程序中。为此，RPLC和HILIC均可推荐使用。
