AbstractIntroductionShengmai San, a well‐known traditional Chinese medicine formula, is used to treat coronary heart diseases and myocardial infarction. The complex composition and complicated mechanism of the Shengmai preparations bring a significant challenge in the development of a suitable quality control method.ObjectivesThis work aims to establish a chromatographic fingerprinting method and propose a weighting algorithm for application in fingerprint similarity analysis to ensure consistent quality of the Shengmai capsule.MethodologyA chromatographic fingerprint method was established using tandem UV/charged aerosol detection (CAD) for Shengmai capsule quality control. After method verification, the developed method was applied to analyze 15 batches of the samples. Then a weighting algorithm of the fingerprint peak was proposed and used for the fingerprint similarity analysis.ResultsAn HPLC‐UV/CAD fingerprint method was successfully developed for the Shengmai capsules. Chromatographic conditions of the HPLC‐UV/CAD method were optimized with a definitive screening design, and the optimized ranges of operating parameters were obtained with a Monte Carlo simulation method. The combined use of the proposed weighting algorithm and similarity analysis on fingerprint data improves the sensitivity of distinguishing batch‐to‐batch quality differences.ConclusionThe developed HPLC‐UV/CAD fingerprint method is robust, reliable, and efficient. The proposed weighting algorithm combined with similarity analysis is promising and meaningful for the quality consistency assessment of HPLC‐UV/CAD fingerprints.