OBJECTIVE:To establish a method for determination of leflunomide using reversed-phase high performance liquid chromatography.METHODS:Chromatographic conditions included Hypersil ODS C₁₈column and the mobile phase consisting of a mixture of methanol-water-phosphoric acid.Detection wavelength was at 260 nm.The flow rate was 1.0 ml·min^-1.Naphthalene or p-phenylphenol was selected as the internal standard.RESULTS:When naphthalene was used as the internal standard,the linearity between concentration and peak area ratio was obtained from 0.0955μg·ml^-1to 7.6400μg·ml^-1(r=0.9999),the detection limit was 0.8ng,within-day and between-day variation coefficients were 0.76% (n=5) and 0.86%(n=5),the average recovery was 99.66% (RSD=0.80%).When p-phenylphenol was used as the internal standard,the linearity between concentration and peak area ratio was obtained from 0.141μg·ml^-1 to 8.460μg·ml^-1(r=0.9997),the detection limit was 0.8ng,within-day and between-day variation coefficients were 0.86% (n=5) and 1.06%(n=5),the average recovery was 100.48% (RSD=1.60%).CONCLUSION:The method was found to be simple and accurate.