4.6 Article

Rapid characterization of the potential active metabolites of diacerein in rat plasma based on UHPLC-Q-exactive orbitrap mass spectrometry and molecular docking

出版社

ELSEVIER
DOI: 10.1016/j.jpba.2023.115447

关键词

Metabolites; Diacerein; Characterization; UHPLC-Q-Exactive Orbitrap Mass Spectrometry; Molecular docking

向作者/读者索取更多资源

In this research, a method combining ultra-high-performance liquid chromatography and mass spectrometry was used to detect the active metabolites of diacerein in rat plasma. A total of 32 metabolites were identified, among which 31 were newly discovered. The metabolites showed various reactions in the body, and two metabolites, M21 and M1, showed strong affinity with IL-1 receptors, indicating their potential as active metabolites of diacerein.
Diacerein, a competently semisynthetic diacetyl derivative of anthraquinone, is a nonsteroidal anti-inflammatory drug, which has been used for treating osteoarthritis and preventing vascular diseases. However, previous investigation indicated that diacerein metabolites and its metabolic pathway in vivo was still unclear. In this research, an effective method was established based on ultra-high-performance liquid chromatography coupled with Q-Exactive-Orbitrap mass spectrometer and molecular docking to screen and detect the potential active metabolites of diacerein in rat plasma after oral administration. The data acquisition and processing methods including Full MS-ddMS2 combined with parallel reaction monitoring mode, extracted ion chromatogram and diagnostic fragment ions were adopted to detect and identify more infinitesimal and unknown diacerein metabolites in vivo. As a result, a total of 32 metabolites were detected and identified in rat plasma according to retention times, accurate mass, diagnostic fragment ions, and relevant drug biotransformation knowledge, among 31 metabolites were firstly reported in this study. Then, the relevant reactions in vivo such as deacetylation, hydroxylation, methylation, sulfate conjugation, glucuronidation, and their composite reactions, were all detected. Ultimately, the results of molecular docking showed that the metabolites of diacerein might have good affinity with IL-1 receptor in vivo. Among them, the metabolites M21 and M1 have the strongest binding affinity with IL-1 receptors, and could be considered as potential active metabolites of diacerein, which have an efficient effect on exerting pharmacological effects of diacerein in vivo. In conclusion, the study of diacerein metabolites in rat plasma expanded our understanding about the metabolism of diacerein in vivo and provided the significant foundation for further drug efficacy studies.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据