UHPLC-Q-Exactive Orbitrap MS Analysis of Shentong Zhuyu Decoction: From Chemical Constituents to Serum Metabolites

Shentong Zhuyu Decoction (STZYD) is a classical Traditional Chinese Medicine (TCM) formula widely used for Rheumatoid arthritis (RA). However, its chemical composition and in vivo metabolic profile remain largely unclear. This study aims to characterize the chemical material basis of STZYD. We analyzed the components, absorbed prototype constituents, and metabolites of STZYD using serum pharmacology-based ultra-performance liquid chromatography coupled with Quadrupole-Orbitrap Mass Spectrometry (UHPLC-Q-Exactive Orbitrap-MS). A total of 1,024 compounds were identified in STZYD, including 165 phenylpropanoids, 162 terpenes, 150 flavonoids, and 98 carbohydrates/glycosides. In medicated serum, we detected 104 absorbed prototype constituents (e.g., gentiopicroside and nodakenin) and 46 metabolites (comprising 7 Phase I, 10 Phase II, and 29 combined Phase I/II metabolites). This study systematically characterized the chemical profile and in vivo metabolites of STZYD using high-resolution MS. These findings clarify the potential material basis responsible for the therapeutic effects of STZYD against RA.