Abstract: In order to assess the stability of sulfa drug in aquatic organization and factors that affect the test results, quality control testing technology research had been carried out. The environmental conditions from sampling to test process had been simulated. Shrimp spiked samples in 3 concentrations (40 μg/kg, 50 μg/kg, 70 μg/kg) under 4 different storage conditions (treated under repeated freezing, thawing and cryopreservation processing) were tested. At the same time, inter-laboratory comparison of 2 designated detection methods had been carried out: the Ministry of Agriculture Bulletin No.958 -12-2007 (reverse phase high-performance liquid chromatography) and the Ministry of Agriculture Bulletin No.1077 -1-2008 (liquid chromatography tandem mass spectrometry). The results showed that, there was no significant difference between the experimental groups, the recoveries of sulfadiazine, sulfa-merazine, sulfa-methazine, sulfadimoxine in different concentrations was between 71.2%-98.9%, the stability of 4 sulfa drugs in aquatic organizations are strong. 2 detection methods could meet the test requirements, reasonable choice of detection method before inspection should follow the actual needs of samples and methods applicable range, to ensure accurate and reliable detection results.