Global characterization of chemical compounds in Shidan granule and their metabolites in rat plasma using ultra-high-performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry.

Shidan granule is an in-hospital traditional Chinese medicine prescription with obvious clinical effects in the treatment of chronic atrophic gastritis. Characterizing the compounds of Shidan granule and exploring the absorbed prototype constituents and metabolites in the blood is significant to understand its effective compounds. In this work, a reliable approach based on ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry was performed for systematic analysis of chemical substances of Shidan granule and their metabolites in rat plasma. The compounds were rapidly characterized using integrated filtering methods, including mass defect filtering, neutral loss filtering, and diagnostic fragment ions filtering. As a result, 87 compounds were tentatively or unambiguously characterized. In rat plasma, a total of 79 components, including 21 prototype constituents and 58 metabolites, were preliminarily determined. And flavonoids-related, phenolic acids-related, saponins-related and terpenoids-related compounds were the main precursors of these metabolites. Phase I reactions (methylation, demethylation, hydroxylation, hydrogenation, and oxidation) and phase II reactions (glucuronidation, glucosidation, and sulfation) were observed as the major metabolic pathways of Shidan granule. It is the first comprehensive study on the metabolism of Shidan granule in vivo, which could offer a solid scientific basis for exploring the multiple effects and therapeutic mechanisms of Shidan granule.