Abstract: An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for simultaneous determination of 23 sulfonamide drugs residues in chicken. The samples were extracted by 80% acetonitrile solution (containing 0.2% formic acid) and the extracts were purified on Oasis PRiME HLB solid-phase extraction column. The 23 sulfonamide drugs were analyzed by Waters Acquity UPLC CSH C18 column (100 mm×2.1 mm, 1.7 μm) using methanol and 0.1% formic acid as the mobile phases, electrospray source positive ion scanning and retention time-dependent multiple reaction monitoring mode (Scheduled MRM) detection, external standard method for quantification. The results showed that there was a good linear relationship between 23 sulfonamide drugs in the linear range of 0.2~20 ng/mL, with the correlation coefficients all greater than 0.9996. The detection limits were 0.1~2.0 μg/kg, and the quantification limits were 0.25~5.0 μg/kg. The average recovery rates were 66.12%~99.83% and the relative standard deviations (RSD, n=6) form 0.72% to 10.36% at the three standard levels of 1.0, 2.0 and 5.0 μg/kg. The method is simple, sensitive and reproducible. The method is successfully used for accurate and quantitative measurement of multiple sulfanilamide drugs residues in chicken.