Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
ADSI-Austrian Drug Screening Institute GmbH, University of Innsbruck, Innrain 66a, 6020 Innsbruck, Austria.
Chem Res Toxicol. 2021 Dec 20;34(12):2522-2533. doi: 10.1021/acs.chemrestox.1c00288. Epub 2021 Dec 8.
Capsaicin, primarily known as the pungent ingredient in hot peppers, is rapidly metabolized in the human body by enzymatic processes altering the pharmacological as well as toxicological properties. Herein, the oxidative transformation of capsaicin was investigated with electrochemistry as well as human liver microsomal incubations. The reaction mixtures were analyzed with liquid chromatography-mass spectrometry. Structure elucidation involved accurate mass measurements and multistage tandem mass spectrometry experiments. In total, 126 transformation products were detected. Electrochemistry provided evidence for 101 transformation products and the microsomal incubations for 46 species. 21 compounds were observed with both approaches. Identified oxidative pathways likely occurring during the phase I metabolism included dehydrogenation, O-demethylation, and hydroxylation reactions as well as combinations thereof. Furthermore, trapping of reactive intermediates either with glutathione or with electrochemically activated ribonucleosides provided evidence for the possible production of phase II metabolites and covalent adducts with a genetic material. Evidence for the occurrence of some capsaicin metabolites in humans was obtained by urine screening.
辣椒素主要作为辣椒中的辛辣成分而被人们所熟知，它在人体内可通过酶促反应迅速代谢，从而改变其药理学和毒理学性质。本文采用电化学和人肝微粒体孵育的方法研究了辣椒素的氧化转化。反应混合物采用液相色谱-质谱联用技术进行分析。结构确证涉及精确质量测量和多级串联质谱实验。共检测到 126 种转化产物。电化学方法提供了 101 种转化产物的证据，而微粒体孵育则提供了 46 种产物的证据。两种方法均观察到 21 种化合物。可能发生在 I 相代谢过程中的氧化途径包括脱氢、O-去甲基化和羟化反应以及它们的组合。此外，用谷胱甘肽或电化学激活的核苷捕获反应性中间体为可能产生 II 相代谢物和与遗传物质形成共价加合物提供了证据。通过尿液筛查获得了一些辣椒素代谢物在人体中存在的证据。
