A rapid and efficient multiresidue method that involves using improved QuEChERS method and liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS) was developed to measure trace levels of sulfonamides in fish tissue. This proposed method was proven to be a powerful, highly sensitive, and environmentally friendly analytical tool that requires minimal sample preparation. The typical MS/MS fragmentation patterns of the [M+H](+) were 156 m/z, 108 m/z, and 92 m/z. Separation was performed on HC-C18 columns with a gradient elution by using methanol -5 mM ammonium acetate containing formic acid (pH 3.5). This method was validated and exhibited favorable performance as well as acceptable accuracy (80.2-93.5%), precision (3.82-8.71%), sensitivity (limits of detection (LODs) 0.43-1.22 mu g kg(-1), limits of quantification (LOQs) 1.27-3.71 mu g kg(-1); decision limit (CC alpha) 1.49-10.9 mu g kg(-1), detection capability (CC beta) 1.71-11.4 mu g kg(-1)), and an acceptable matrix effect (-18.2-18.4%). This methodology has been successfully applied in analyzing various fish tissue from local markets. (c) 2014 Elsevier Ltd. All rights reserved.