Abstract: Objective： To establish an UPLC-MS/MS method for determining the content of domperidone. Methods：The determination was performed on a column Agilent ZORBAX Eclipse Plus C18(2.1 mm×50 mm，5 μm) with a mixture of 0.1% formic acid and acetonitrile as mobile phase，the flow rate was 0.3 mL·min-1， the column temperature was 40 ℃ and the injection volume was 2 μL. MS conditions： Electrospray ionization source， positive ion monitoring mode(ESI+)， the nebulizer pressure was 45psi， the dry gas flow rate was 8.0 mL·min-1， the dry gas temperature was 300 ℃， the sheath gas flow rate was 10.0 mL·min-1， the sheath gas temperature was 325 ℃， the gas was high purity nitrogen， the ion source voltage was 5 500 V and the scan mode was MRM multi-reaction monitoring scan. Results：A good linearity was obtained in high concentration range of 1.012~10.12 μg· mL-1 of domperidone and the average recovery was 97.79%(RSD=1.5%)， in addition， a good linearity was obtained in low concentration range of 0.506 0~50.60 μg·L-1 of domperidone and the average recovery was 95.73%(RSD=1.3%). Conclusion：The method was fast， simple， specific and sensitive.It can provide a theoretical basis for the research of quality standards of domperidone.