Department of Analytical Chemistry, Israel Institute for Biological Research (IIBR), Ness Ziona, Israel.
Rapid Commun Mass Spectrom. 2024 Oct 30;38(20):e9881. doi: 10.1002/rcm.9881.
Tramadol (T) is a strong painkiller drug that belongs to the opioid analgesic group. Several accidental intoxication cases after oral administration of T have been reported in the past decade. Tramadol, its derivatives, and metabolites present information-limited mass spectra with one prominent peak representing the amine-containing residue; therefore, their structural determination based on both electron impact mass spectrometry (EI-MS) and ESI-MS/MS spectra could be misleading.
A novel analytical method for the structural elucidation of tramadol, its four homologs, and its two main phase I metabolites (N-desmethyltramadol and O-desmethyltramadol) was developed using chemical modification and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS) with Orbitrap technology.
After chemical derivatization, each of the investigated T series exhibited informative mass spectra that enabled better exposition of their structures. The developed method was successfully implemented to explicitly identify the structures of tramadol and its N-desmethyltramadol metabolite in urine samples at low ng/mL levels.
An efficient derivatization-aided strategy was developed for rapidly elucidating the structure of tramadol-like compounds. The method is intended to assist forensic chemists in better diagnosing T and its analogs and metabolites in clinical or forensic toxicology laboratories.
曲马多（T）是一种强效止痛药，属于阿片类镇痛药。在过去十年中，有报道称口服 T 后发生了几例意外中毒病例。曲马多、其衍生物和代谢物的质谱信息有限，仅具有一个代表含胺残留物的突出峰；因此，基于电子轰击质谱（EI-MS）和电喷雾串联质谱（ESI-MS/MS）谱图进行结构鉴定可能会产生误导。
本研究开发了一种新的分析方法，用于使用化学修饰和具有 Orbitrap 技术的液相色谱-高分辨率串联质谱（LC-HR-MS/MS）对曲马多、其四个同系物及其两个主要的 I 相代谢物（去甲基曲马多和去甲氧基曲马多）进行结构阐明。
化学衍生化后，所研究的 T 系列中的每一种都表现出信息丰富的质谱，能够更好地揭示其结构。所开发的方法成功地用于在低 ng/mL 水平下明确鉴定尿液样品中的曲马多及其 N-去甲基代谢物的结构。
本研究开发了一种有效的衍生化辅助策略，用于快速阐明类似曲马多化合物的结构。该方法旨在帮助法医化学家在临床或法医毒理学实验室更好地诊断 T 及其类似物和代谢物。
