Abstract: OBJECTIVE To establish a method for determination of the six residual organic solvents(methanol, ether, dichloromethane, ethyl acetate, 1,4-dioxane and N,N-dimethylformamide) in ambrisentan. METHODS Gas chromatography with headspace sampling was applied in the study. Agilent DB-624 silica capillary column(30.0 m×0.53 mm, 3.00 μm) was used. The inlet temperature was 250 ℃ and the FID detector temperature was 250 ℃. N₂ was carrier gas at a column pressure of 2 psi. The initial temperature was kept at 50 ℃ for 10 min, then the temperature was raised to 200 ℃ at the rate of 20 ℃·min^-1 and subsequently sustained for 4 min. FID detector temperature was 300 ℃. The vial temperature was 100 ℃, and the vial time was 30 min. RESULTS The linear correlation coefficients of this method for methanol, ether, dichloromethane, ethyl acetate, 1,4-dioxane and N,N-dimethylformamide were 0.999 6, 0.999 2, 0.999 5, 0.999 3, 0.999 3 and 0.999 6, respectively. The RSDs of precision and repeatability were all <5.0%. The limits of detection were 0.36, 0.034, 0.51, 0.43, 0.45 and 5.27 μg·mL^-1, respectively. The average recovery were >90%. The sample solution was stable in 24 h. CONCLUSION The analytical method is simple, accurate and sensitive, and is suitable for the determination of residual solvents in ambrisentan.