OBJECTIVE: To determine residual citrinin in Zhibituo tablet by solid phase extraction-UPLC-MS/MS. METHODS: The sample was processed preliminary by solid extraction. The determination was performed on Zorbax Eclipse Plus C18 column with mobile phase consisting of water (0.1% formic acid)-acetonitrile (70 ∶ 30,V/V, gradient elution) at the follow rate of 0.30 mL/min. The column temperature was 40 ℃, and analysis time was 7 min, the sample size was 2 μL. Ionization mode was positive ion mode. The ion source temperature was 150 ℃, drying gas velocity was 15 L/min, sheath gas temperature was 350 ℃,sheath gas flow rate was 12 L/min, capillary voltage was 3 500 V, atomization device pressure was 40 psi, atomization voltage was 0 V. The acquisition mode was MRM mode. RESULTS: The linear range of citrinin was 0.1-20 ng/mL(r=0.999 4); the limits of quantitation and detection were 0.05 and 0.01 ng/mL. RSDs of precision, stability and repeatability tests were all lower than 2.0%; recoveries were 98.868%-103.160% (RSD=1.5%,n=6). CONCLUSIONS: The method is rapid, sensitive, accurate and suitable for the determination of residual citrinin in Zhibituo tablet.