Integrated UHPLC‐MS/MS and DrugCIPHER‐Based Network Pharmacology to Identify Signature Components and Evaluate Pharmacokinetics of Biyuan Tongqiao Granules in Rats

Biyuan Tongqiao Granules (BTG) is commonly used TCM formula for the clinical treatment of acute rhinosinusitis (ARS). However, the systemic identification of its plasma-absorbed components and metabolites, as well as the pharmacokinetic profiles of its pharmacodynamically relevant signature compounds, remains poorly characterized. In this study, UHPLC-Q-Orbitrap HRMS was first employed to identify prototype components and their metabolites in rat plasma after intragastric administration of BTG. An integrated strategy combining DrugCIPHER-based network pharmacology and UHPLC-QTRAP-MS/MS was subsequently developed and applied to screen signature compounds for ARS treatment and investigate the pharmacokinetic behaviors of these signatures in rat plasma. A total of 38 prototype components and seven metabolites were unambiguously identified. Based on the potential targets and enriched pathways in network pharmacology analysis, six signature compounds (caffeic acid, baicalin, oxypeucedanin hydrate, luteolin, wogonoside, and wogonin) were screened, and a sensitive UHPLC-QTRAP-MS/MS method was established, which revealed that caffeic acid exhibited rapid absorption, whereas the other five components showed delayed absorption characteristics, and all detected compounds presented short elimination half-lives. This integrated analytical workflow provides a chemical and pharmacokinetic basis for further research and rational clinical use of BTG in ARS.