Standard method validation is an important part of the quality management process in inspection and testing laboratories, and is the foundation for ensuring the accuracy of inspection and testing data. In this study, a method for determination of sulfonamides residues in water by UPLC-MS/MS was established. Verify the method from standard curve, linear range, quantification limit, precision, and method recovery rate. And the key experimental points of this method were analyzed and optimized. 17 kinds of sulfonamides had good linearity within the concentration range of 5.0~50.0 ng/mL. The correlation coefficient of calibration curve was more than 0.997. The detection limit of this method was 0.038 ng/mL. The average recovery rates of three spiked levels ranged from 74.6% to 105.6%, and the relative standard deviations were 0.89%~12.89%. This method was applied to detect the residues of sulfonamide drugs in water samples and aquaculture pond water samples in Jiading District, Shanghai. The establishment of this method can provide technical basis for monitoring the residues of sulfonamide drugs in rivers and aquaculture water.[Chinese Fishery Quality and Standards,2024,14(2):07-13]