Abstract: The non-standard drug sample for aquaculture (1.00 g) was taken, and 10 μL of 1.0 mg·L^-1 prometryne-d₆ (internal standard) solution and 20 mL of water were added. The solid sample was centrifuged for 5 min after homogenization and ultrasonication, while the liquid sample was centrifuged for 5 min after stirring well by vortex oscillation, both in which the supernatant was taken and made its volume up to 100 mL with water. The aquaculture water sample was filtered through a 0.45 μm filter membrane, 200 mL of the filtrate was taken, and 10 μL of 1.0 mg·L^-1 of prometryne-d₆ solution was added, shaking and mixing well. The above sample solution was passed through NPO HLB solid phase extraction column (activated with 5 mL of methanol and 5 mL of water), washed with 5 mL of water, and eluted with 6 mL of methanol. The eluent was blown to near dryness at 40 ℃ by nitrogen. The residue was redissolved in 1.0 mL of a mixture of methanol and 2 mmol·L^-1 ammonium acetate solution containing 0.1% (volume fraction, the same below) formic acid at a volume ratio of 3∶7. After vortex, ultrasonic oscillation, centrifugation and filtration, the residues of prometryne, avermectin and ivermectin were determined by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS), using Waters ACQUITY UPLC C₁₈ column as stationary phase and mixtures of methanol and 2 mmol·L^-1 ammonium acetate solution containing 0.1% formic acid at different volume ratios as mobile phase for gradient elution. Electrospray ion (ESI) source was used for mass spectrometry, with multiple reaction monitoring mode in positive scanning mode. Internal standard method was used for quantitative analysis. As shown by the results, the linear ranges of the standard curve were 0.2-15.0 μg·L^-1for prometryne, and 2.0-150.0 μg·L^-1 for avermectin and ivermectin, with detection limits (3S/N) of 0.2, 2.0, 2.0 μg·kg^-1 respectively in the non-standard drug samples, and 1.0, 10, 10 μg·L^-1respectively in water samples. Test for recovery was made by standard addition method, giving results in the range of 84.8%-105%, with RSDs (n=6) of the determined values less than 9.0%. This method was applied to the analysis of 80 actual samples, and it was shown that avermectin was detected with a residue of 718 mg·kg^-1 in a non-standard drug sample, and prometryne was detected with a residue of 3.2 ng·L^-1 in a water sample.