Department of Clinical Pharmacology and Pharmacoepidemiology, Im Neuenheimer Feld 410, University Hospital Heidelberg, Germany.
UMR8203 "Vectorologie & Thérapeutiques Anticancéreuses", CNRS, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France; Département de Cancérologie de l'Enfant et de l'Adolescent, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France.
J Pharm Biomed Anal. 2018 Mar 20;151:151-158. doi: 10.1016/j.jpba.2017.12.056. Epub 2017 Dec 28.
Metabolite reference standards are often not available, which results in a lack of MS/MS spectra for library matching. Consequently, the identification of suspected metabolites proves to be challenging. The present study aims at structurally elucidating the MS/MS fragmentation behavior of selected benzimidazole anthelmintics to theoretically predict characteristic product ions for rapid and systematic tentative metabolite identification. A set of common characteristic product ions was identified from accurate mass MS/MS experiments for five parent compounds. It was hypothesized that the mass shift of any metabolic transformation at the parent molecule also is observable in the mass spectrum of the corresponding metabolite. This was tested and verified with six metabolite reference standards and subsequently, formulated as a general prediction scheme. The approach was integrated into a rapid MS QTOF workflow and tested in mouse plasma for mebendazole and its metabolites. The presented scheme allows the prediction of characteristic product ions for suspected unknown metabolites. These can be matched with measured product ions of suspected metabolites for tentative identification. The theoretically predicted spectra can contribute to the tentative identification of unknown compounds in non-target and suspect screening approaches.
代谢物标准品通常不可用，这导致用于库匹配的 MS/MS 谱图缺乏。因此，鉴定可疑代谢物具有一定的挑战性。本研究旨在阐明选定苯并咪唑类驱虫药的 MS/MS 碎裂行为，从理论上预测特征产物离子，以快速系统地进行初步代谢物鉴定。从 5 种母体化合物的精确质量 MS/MS 实验中鉴定出了一组常见的特征产物离子。假设母体分子上任何代谢转化的质量位移在相应代谢物的质谱中也可以观察到。这通过 6 个代谢物标准品进行了测试和验证，并随后提出了一个通用的预测方案。该方法被整合到快速 MS QTOF 工作流程中，并在小鼠血浆中对苯并咪唑及其代谢物进行了测试。所提出的方案允许对可疑未知代谢物的特征产物离子进行预测。这些可以与可疑代谢物的实测产物离子进行匹配，进行初步鉴定。理论预测的谱图有助于在非靶向和可疑筛选方法中对未知化合物进行初步鉴定。
