School of Chemistry and Chemical Engineering, Guangxi University, 100 Daxue Dong Road, Nanning, Guangxi 530004, China.
Guangxi Colleges and Universities Key Laboratory of Applied Chemistry Technology and Resource Development, Guangxi University, 100 Daxue Dong Road, Nanning, Guangxi 530004, China.
J Anal Toxicol. 2023 May 19;47(5):436-447. doi: 10.1093/jat/bkad021.
In this study, we used solid-phase extraction with liquid chromatography-ion trap time-of-flight mass spectrometry (LC-IT-TOF-MS) to analyze 2-fluorodeschloroketamine (2-FDCK) metabolites in human urine. The complete set of oxidative metabolites was identified, with 17 compounds divided into four groups. Furthermore, we examined the hydroxy substitution site after oxidative metabolism with theoretical calculation and 2-FDCK nuclear magnetic resonance (NMR) data. We clarified the correlation of the oxidative metabolic sites with the electron cloud density in the structure. Additionally, two enantiomers of dihydro-2-fluorodeschloroketamine (dihydro-2-FDCK) were determined by using a laboratory-made dihydro-2-FDCK hydrochloride reference substance. Their configurations were determined via NMR spectrometry data prediction of the ACD Labs-Structure Elucidator Suite software and theoretical calculation. Moreover, the stereoselectivity of the related enzymes in hydrogenation metabolism in vivo was clarified. These findings provide an important reference for analyzing other oxidative metabolites, laying the foundation for future analysis, prediction, elucidation and identification of the latest ketamine-type new psychoactive substance metabolites.
在这项研究中，我们使用固相萃取-液相色谱-离子阱飞行时间质谱联用技术（LC-IT-TOF-MS）分析了人尿液中的 2-氟代去氯氯胺酮（2-FDCK）代谢物。鉴定了完整的氧化代谢物组，共 17 种化合物分为四组。此外，我们通过理论计算和 2-FDCK 核磁共振（NMR）数据研究了氧化代谢后的羟取代部位。我们阐明了氧化代谢部位与结构中电子云密度的相关性。另外，使用实验室自制的二氢-2-FDCK 盐酸盐参考物质，确定了二氢-2-氟代去氯氯胺酮（dihydro-2-FDCK）的两种对映异构体。通过 ACD Labs-Structure Elucidator Suite 软件的 NMR 光谱数据预测和理论计算确定了它们的构型。此外，阐明了体内氢化代谢相关酶的立体选择性。这些发现为分析其他氧化代谢物提供了重要参考，为未来分析、预测、阐明和鉴定最新的氯胺酮类新型精神活性物质代谢物奠定了基础。
