OBJECTIVE: To establish a method for simultaneous determination of 3 active components as codeine phosphate, ephedrine hydrochloride, chlorphenamine maleate and 2 preservatives as sodium benzoate and ethylparaben in Compound codeine phosphate oral solution. METHODS: HPLC method was adopted. The determination was performed on GL·Science WondaSil C18-WR column with mobile phase consisted of acetonitrile-0.01 mol/L potassium dihydrogen phosphate solution (containing 2.5 mmol/L sodium heptane sulfonate and 0.1% triethylamine, pH adjusted to 2.5±0.1 with phosphoric acid) (gradient elution) at the flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm and column temperature was 30 ℃. The sample size was 10 μL. RESULTS: The linear ranges of codeine phosphate, ephedrine hydrochloride, chlorphenamine maleate, sodium benzoate and ethylparaben were 0.365 8-457.20 μg/mL (r=0.999 9), 0.363 5-454.35 μg/mL (r=0.999 9), 0.124 8-155.98 μg/mL (r=0.999 9), 0.390 6-488.25 μg/mL (r=0.999 9), 0.121 3-151.65 μg/mL(r=0.999 9), respectively. The limits of quantitation were 0.409 4, 0.508 8, 7.731 4, 1.347 6, 1.940 8 ng; the limits of detection were 0.146 2, 0.181 7, 2.494 0, 0.449 2, 0.606 5 ng. RSDs of precision, stability and reproducibility tests were all lower than 1%. The average recoveries were 98.10%-101.96%(RSD=1.4%,n=9), 97.65%-101.14%(RSD=1.2%,n=9), 97.30%-102.30% (RSD=1.8%,n=9), 97.71%-102.21%(RSD=1.5%,n=9), 97.03%-101.55%(RSD=1.7%,n=9), respectively. CONCLUSIONS: The method is simple, precise, stable and reproducible, and it can be used for simultaneous determination of codeine phosphate, ephedrine hydrochloride, chlorphenamine maleate, sodium benzoate and ethylparaben in Compound codeine phosphate oral solution.