OBJECTIVE To establish the method for the content determination of ephedrine hydrochloride and pseudoephedrine hydrochloride in Shexiang zhuanggu plaster ，and to evaluate the quality of 222 batches of Shexiang zhuanggu plaster from 41 manufacturers. METHODS HPLC method was established. The determination was performed on Shimadzu Shim-pack GIS-C 18 column with mobile phase consisted of acetonitrile- 0.1％ phosphoric acid （3∶97，V/V）at the flow rate of 0.9 mL/min. The column temperature was set at 30 ℃，the detection wavelength was 210 nm，the sample size was 10 μL. Taking the content data of 222 batches of samples as index ，the cluster heatmap was drawn by Hiplot biomedical data visualization and analysis platform. RESULTS The results of the methodological investigation were in line with the requirements of the general principles stated in 2020 edition of Chinese Pharmacopoeia （part Ⅳ ）. The total contents of ephedrine hydrochloride and pseudoephedrine hydrochloride in 222 batches of samples from 41 manufacturers were 0.646-6.325 μg/cm2. Results of cluster heatmap analysis showed that these samples of 41 manufacturers could be divided into 3 categories. The contents of components in samples from different manufacturers varied greatly ，and the contents of components in different batches of samples from the same manufacturers also varied greatly. If the proposed limit of this product was that the total amount of ephedrine hydrochloride and pseudoephedrine hydrochloride per 1 cm2 would not be less than 1.00 μg，23 of the 222 batches of samples were unqualified. CONCLUSIONS The established method for the content determination of ephedrine hydrochloride and pseudoephedrine hydrochloride in Shexiang zhuanggu plaster is accurate and precise ，and can be used for the quality control. Some manufacturers should pay attention to optimizing production process and strengthening quality control.