Traditional solid-phase extraction (SPE) and membrane filtration technology are complicated,and time and labor consuming.In this study,the PRiME and membrane filtration technology were integrated to realize the integration of operational steps before sample injection,and the relevant technical parameters were optimized.A quantitative method for the determination of berberine hydrochloride and robenidine hydrochloride in fish was established by liquid chromatography tandem mass spectrometry.The results showed that berberine hydrochloride and robenidine hydrochloride had good linearity in the range of 0.5-100 g/L,the detection limits (LOD) were 0.51 g/kg and 0.53 g/kg,the quantitative limits (LOQ) were 1.67 g/kg and 1.68 g/kg,the intraday relative standard deviation of precision was 4.09%-4.48% and 3.84%-3.90%,respectively,and the intraday relative standard deviation of precision was 5.17%-5.73% and 4.23%-5.29%,respectively.The recoveries of berberine hydrochloride and robenidine hydrochloride were 91.2%-93.2% and 91.3%-92.4%,respectively,at 5,10,50 g/kg concentrations.The RSD was 4.5%-4.6% and 1.8%-5.2%,respectively.The liquid chromatography-tandem mass spectrometry (LC-MS) was used to determine the residues of target compounds in fresh fish on the market,and no positive samples were detected,indicating that berberine hydrochloride and chlorophenguanidine hydrochloride were used well in aquaculture.