Identification and Multidimensional Evaluation of Quality Markers in Yupingfeng via UPLC‐Q‐Orbitrap‐MS, Network Pharmacology, UPLC‐UV Fingerprint, and UPLC‐QQQ‐MS

ABSTRACT Yupingfeng (YPF), a classical traditional Chinese medicine (TCM) formula, is widely used to tonify qi and strengthen the exterior. However, research on the quality control of YPF remains limited. A single indicator is insufficient to comprehensively reflect the quality attributes of this complex TCM system. This study aims to investigate the potential quality markers (Q‐markers) of YPF with multidimensional analysis. First, 28 specific components of YPF were preliminarily identified by UPLC‐Q‐Orbitrap‐MS/MS based on ingredient specificity. Next, the targets of specific ingredients were predicted using SwissTargetPrediction and analyzed with protein–protein interaction network analysis to obtain 71 core targets. The effectiveness was prioritized through systematic ranking based on network pharmacological analysis. Then, common components shared by YPF powder, YPF preparations, and rat serum were characterized using UPLC‐QQQ‐MS and UPLC‐UV. Finally, 10 compounds, including prim‐O‐glucosylcimifugin, calycosin‐7‐O‐glucopyranoside, cimifugin, 5‐O‐methylvisammioside, ononin, sec‐O‐glucosylhamaudol, calycosin, astragaloside A, formononetin, and atractylenolide II, were identified as the Q‐markers of YPF, and a rapid UPLC‐QQQ‐MS method was developed for their simultaneous determination. Overall, the multidimensional analysis based on the “five principles” was first applied to identify the Q‐markers of YPF, thereby providing guidance for the quality control of YPF and its preparations.