医药导报2023，Vol.42Issue(12)：1772-1779,8.DOI:10.3870/j.issn.1004-0781.2023.12.005
托伐普坦在大鼠体内的代谢产物鉴定分析
Identification of In Vivo Metabolites of Tolvaptan in Rats
摘要
Abstract
Objective The metabolites of tolvaptan in rats were identified by ultra-performance liquid chromatography-quadrupole-exactive orbitrap high-resolution mass spectrometry(UFLC-Q-Exactive Orbitrap MS),and the possible metabolic pathways of tolvaptan in rats were discussed.Methods Plasma,urine and fecal samples from rats were collected after a single oral administration of 60 mg·kg-1 tolvaptan solid dispersion solution.The protein in the samples was precipitated with acetonitrile.UFLC-Q-exactive orbitrap MS technology was adopted for the sample analysis and the data were processed by Xcalibur 2.0 software.Results According to the retention time,precise relative molecular mass,characteristic fragment ions and related literature reports of each compound,35 metabolites were identified in rat biological samples.Moreover,23,26 and 30 metabolites in the plasma,urine and feces were identified,respectively.The major metabolic pathways of tolvaptan were identified as hydroxylation,carboxylation,hydrolysis,dehydrogenation,glucuronidation and acetylation.Conclusion Our study confirmed the major metabolites of tolvaptan in rats,enriched the metabolite spectrum of tolvaptan in vivo,and provided an experimental basis for the in-depth study of the pharmacodynamic substance basis of tolvaptan.关键词
托伐普坦/高分辨质谱/代谢产物Key words
Tolvaptan/High-resolution mass spectrometry/Metabolites分类
医药卫生引用本文复制引用
徐国佳,蒋欣,夏滨,斯陆勤,黄建耿,李丹,张永军..托伐普坦在大鼠体内的代谢产物鉴定分析[J].医药导报,2023,42(12):1772-1779,8.基金项目
国家自然科学基金资助项目(81302837,81803834) （81302837,81803834）
湖北省科技厅重点研发计划项目(2020BCB045). （2020BCB045）
