Comprehensive chemical characterization of quanduzhong capsules and In Vivo profiling of parent constituents and metabolites in rats by UPLC-Q-TOF-MSE.

Eucommia ulmoides Oliv. (EU) is a widely used traditional Chinese medicinal herb for tonifying the liver and kidney and strengthening bones and muscles. However, the chemical complexity of Eucommia ulmoides-derived preparations and the low abundance of exogenous components in vivo pose significant challenges for comprehensive characterization. In this study, an integrated qualitative strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry with MSE acquisition (UPLC-Q-TOF-MSE) and the UNIFI platform was established to systematically characterize the chemical constituents of Quanduzhong Capsules and profile their in vivo exposure. A total of 114 compounds were characterized in the methanolic extract, including 27 lignans, 25 iridoids, 30 phenolic acids, 11 flavonoids, 4 terpenoids, and 17 other minor constituents. Following oral administration, 9, 18, and 11 parent constituents were detected in rat plasma, urine, and feces, respectively. After removing overlapping constituents among different biological matrices, 18 distinct parent constituents were identified in vivo. Furthermore, 35 metabolites derived from five representative constituents, including geniposide, geniposidic acid, aucubin, pinoresinol di-O-glucopyranoside, and chlorogenic acid, were identified or tentatively characterized, involving major biotransformation pathways such as deglycosylation, hydrolysis, oxidation/reduction, methylation, glucuronidation, and sulfation. This study provides a comprehensive chemical and metabolic dataset for Quanduzhong Capsules and establishes an efficient analytical workflow for the systematic characterization and exposure evaluation of Eucommia ulmoides-based preparations. These findings highlight the selective in vivo exposure of key constituents and provide insight into the exposure-related material basis of Quanduzhong Capsules.