Simultaneous Determination of 11 Major Components in Renshen Guben Oral Liquid by Ultrahigh‐Performance Liquid Chromatography‐Tandem Mass Spectrometry

ABSTRACT Renshen Guben oral liquid, a traditional Chinese medicine derived from Liuwei Dihuang Pill, is widely used for symptoms associated with Qi and Yin deficiency. However, its complex multi‐herbal composition complicates quality assessment; existing methods relying on limited marker compounds are insufficient to reflect its pharmacological basis. This study developed a robust and sensitive UHPLC‐MS/MS method for the simultaneous determination of 11 representative active constituents, including ginsenosides, paeonol, and catalpol. Guided by Analytical Quality by Design principles, chromatographic conditions, and MS parameters were optimized to ensure selectivity and sensitivity. The method achieved complete separation within 15 min of run time and exhibited excellent linearity ( R 2 ≥ 0.9899), low quantification limits (1–50 ng/mL), and acceptable precision and accuracy (relative standard deviations ≤ 15%; recoveries 87.5%–113.7%). Evaluation using Analytical Eco‐Scale and AGREE tools yielded favorable green chemistry scores. The method was successfully applied to five batches of samples, revealing batch‐to‐batch variability, particularly in ginsenosides and paeonol content, suggesting that raw material source and processing may impact consistency. This UHPLC‐MS/MS method provides a comprehensive tool for quality control of complex herbal preparations and supports further pharmacological and pharmacokinetic investigations.