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

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.

A Systematic Method for the Identification of Aporphine Alkaloid Constituents in Sabia schumanniana Diels Using UHPLC-Q-Exactive Orbitrap/Mass Spectrometry

Sabia schumanniana Diels (SSD) is a plant whose stems are used in traditional folk medicine for the treatment of lumbago and arthralgia. Previous studies have revealed chemical constituents of SSD, including triterpenoids and aporphine alkaloids. Aporphine alkaloids contain a variety of active components, which might facilitate the effective treatment of lumbago and arthralgia. However, only 5-oxoaporphine (fuseine) has been discovered in SSD to date. In this study, we sought to systematically identify the aporphine alkaloids in SSD. We established a fast and reliable method for the detection and identification of these aporphine alkaloids based on ultra-high-performance liquid chromatography (UHPLC)-Q-Exactive-Orbitrap/mass spectrometry combined with parallel reaction monitoring (PRM). We separated all of the analyzed samples using a Thermo Scientific Hypersil GOLD™ aQ C18 column (100 mm × 2.1 mm, 1.9 µm). Finally, we identified a total of 70 compounds by using data such as retention times and diagnostic ions. No fewer than 69 of these SSD aporphine alkaloids have been reported here for the first time. These findings may assist in future studies concerning this plant and will ultimately contribute to the research and development of new drugs.