Abstract: OBJECTIVE To establish an HPLC method for simultaneous determination of three components (paracetamol, chlorphenamine maleate and caffeine) of compound paracetamol and amantadine hydrochloride capsules, and applied this method to investigate the above three components’ differences of dissolution rate in vitro. METHODS Using Alltima C₁₈ (4.6 mm×150 mm, 5 μm) chromatographic column, mobile phase was methanol-KH₂PO₄ (0.05 mol·L^-1, pH 3.0)-triethylamine (20∶80∶0.02) and flow rate was 1 mL·min^-1, detected at 216 nm. The dissolution rate was measured by rotating basket method, applied 1 000 mL water as dissloution medium80 r·min^-1, (37±0.5)℃, calculated cumulative dissolution percentage of each component at different time, then used similarity factor to compare the similarity of dissolution curve. RESULTS The linearity range of paracetamol, chlorphenamine maleate and caffeine were 2.50-250.10, 0.20-19.50 and 0.61-60.74 μg·mL^-1, and their correlation coefficient (r) were 1.000, 1.000, and 0.999 9, compared with paracetamol, chlorpheniramine maleate and caffeine’s similarity factors were 34 and 73. CONCLUSION The HPLC method is simple, accurate and reproducible and can be used to control the quality of the preparation, the determination of dissolution results show that the above three components don’t all have characteristics of synchronous dissolution.