Identification of In Vivo Metabolites of Tolvaptan in Rats
10.3870/j.issn.1004-0781.2023.12.005
- VernacularTitle:托伐普坦在大鼠体内的代谢产物鉴定分析
- Author:
Guojia XU
1
,
2
,
3
;
Xin JIANG
;
Bin XIA
;
Luqin SI
;
Jiangeng HUANG
;
Dan LI
;
Yongjun ZHANG
Author Information
1. 石河子大学药学院,石河子 832003
2. 石河子大学第一附属医院药学部,石河子 832008
3. 华中科技大学同济医学院药学院,武汉 430030
- Keywords:
Tolvaptan;
High-resolution mass spectrometry;
Metabolites
- From:
Herald of Medicine
2023;42(12):1772-1779
- CountryChina
- Language:Chinese
-
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.
