Abstract: OBJECTIVE To establish an UPLC-MS method for simultaneous determination of 16 kinds of phthalates in film-coated tablets. METHODS Phthalates were extracted with methanol. Separation was performed on Waters ACQUITY UPLC BEH C₁₈ column (2.1 mm×50 mm, 1.7 μm) connected in series with Waters PFCs Isolator column (2.1 mm×50 mm). 0.1% formic acid solution and methanol were used as mobile phases in gradient elution, flow rate was 0.4 mL·min^-1. ESI⁺ and multi-reaction monitoring (MRM) were adopted in MS/MS. RESULTS Sixteen kinds of phthalates could be completely separated. The detection limits of DBP and DIBP were 0.5 mg·kg^-1, and other 14 kinds of phthalates were 0.1 mg·kg^-1. DBP and DIBP in the range of 0.20-1.00 μg·mL^-1, and other 14 kinds of phthalates in the range of 0.05-1.00 μg·mL^-1 had good linear relationships with relative coefficients (r ≥ 0.995). The average recoveries were from 83% to 115%. CONCLUSION The method is simple, rapid and accurate, and can be applied to simultaneous determination of phthalates in film-coated tablets.