Abstract: OBJECTIVE To establish a sensitive method to determine the organic residual solvents in Ketoconanzale. The interaction between organic solvents and ILs was preliminarily explored, intending to provide a basis for choosing suitable ILs as headspace solvent to determinate the residual solvents. METHODS 0.01 g of ketoconanzale were put in a 10 mL headspace vial, followed by spiking 1 mL of ILs. The headspace vial was sealed and radiated under 150 W of microwave power for 75 s to accelarate the dissolution of Ketoconanzale. The sample solution was mainteined at the equilibration temperatute of 110 ℃ for 30 min and a volume of 1 mL headspace gas was directly injected into GC for analysis. A phenomenex ZB-1 capillary column (0.53 mm×60 m) with 5.00 μm film thickness was utilized for chromatographic separation of the solvents with FID as detector. A temperature programme was also employed. RESULTS An excellent seperation of ethanol, dichloromethane, ethyl acetate, butyl alcohol, pyridine, DMF and DMSO was achieved. The calibration curve was linear in the range of 1.25-200 mg·L^-1 for ethanol, 1.50-24.0 mg·L^-1 for dichloromethane, 12.5-200 mg·L^-1 for ethyl acetate, 12.5-200 mg·L^-1 for butyl alcohol, 0.500-8.00 mg·L^-1 for pyridine, 2.20-3.52 mg·L^-1 for DMF and 12.5-200 mg·L^-1 for DMSO. All the average recovery were limited in 89.8%-98.2% and RSD were less than 4.0%. For ethyl, the headspace efficiency of ILs increased with the growth of cation alkyl chain. For ethyl, DMF and DMSO, the headspace efficiency of ILs decreased with the growth of cation alkyl chain. However, the anion of ILs has minor impact on headspace efficiency. Ultimately, BmimPF6 was chosen as the best headspace solvent. CONCLUSION The proposed method is easy, fast and sensitive. It is suitable for the simultaneous determination of ethanol, dichloromethane, ethyl acetate, butyl alcohol, pyridine, DMF and DMSO in Ketoconanzale, providing a new mean for the detection of residual solvent with high-boiling point. The headspace efficiency of ILs increased with the decrease of the cationic polarity for protic solvents and reduced with the decrease of cation polarity for aprotic solvents with nucleophilic ability, while the polarity of the anion has little influence on headspace efficiency. The results above mentioned provides a reference for choosing suitable ILs as headspace solvent to determinate residual solvent.