OBJECTIVE: To establish a method for the determination of related substance in posaconazole raw material. METHODS: HPLC method was adopted. The separation was performed on Zorbax Eclipse Plus C18 column with mobile phase consisted of 0.05 mol/L ammonium acetate solution (pH adjusted to 4.0 using acetic acid)-acetonitrile (gradient elution) at the flow rate of 1.0 mL/min. The detection wavelength was set at 262 nm, and the column temperature was 30 ℃. The sample size was 20 μL. RESULTS: The linear range of intermediateⅠwas 0.05-5.0 μg/mL (r=0.999 9); the limit of quantitation was 0.05 μg/mL, the limit of detection was 0.013 μg/mL; RSDs of precision test, stability test and repeatability test were lower than 2.0%; the recoveries was 98.00%-101.69%(RSD=1.22%,n=9). CONCLUSIONS: The method is simple, accurate and suitable for the determination of related substance in posaconazole raw material.