Abstract: The issue of excessive drug residues in aquatic products restricts the green and high-quality development of China’s fishery industry. Pollution of fishery waters is a major reason for excessive drug residues in aquatic products. Based on the literature and official quality and safety monitoring programs, we selected as target analytes multiple drugs that have been reported to have high detection frequencies in aquatic environments and aquatic products. A comprehensive analytical method was established for the rapid screening of 54 drugs from the classes of sulfonamides, quinolones, macrolides, nitroimidazoles, benzodiazepines, and antiviral drugs in fishery waters by ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）. The pH value of the water samples was adjusted to 3, and the samples were then concentrated and purified on an Oasis HLB solid-phase extraction column, and eluted by 0.02% （V/V） formic acid in acetonitrile. After concentration and purification, 54 target compounds were separated on an ACQUITY Premier HSS T3 chromatographic column using methanol and 0.1% （V/V） formic acid aqueous solution as the mobile phase. The extract was analyzed directly by UPLC-Q-TOF-MS using a dual-spray electrospray ionization source in positive ion mode and quantified by the external standard method. An accurate mass database and a fragment ion library were created for rapid identification and quantification of the 54 drugs in fishery waters. The retention times, accurate masses, isotopic abundances, and isotopic spacings of the principal diagnostic ions for each analyte were used to identify the compounds. For accurate identification, the fragment ion information from the MS/MS profiles of the target analytes was compared with that in the database. For quantification, the exact-mass extracted ion chromatogram （EIC） peak area of each target compound was used. Within the given concentration range, the calibration curves of all 54 target compounds showed good linearity with correlation coefficients no less than 0.995. The recoveries ranged from 61.7% to 107.8%, with relative standard deviations （RSDs） of ≤13.8% （n=3）. The limits of detection （LODs） were 0.5 -5.0 ng/L, and the limits of quantitation （LOQs） were 1.5-15 ng/L. This method exhibits high accuracy and good stability, and is suitable for rapid screening and confirmation of various pharmaceuticals such as antibiotics and antivirals in environmental water bodies, and provides reliable technical support for the monitoring of various drug residues and risk prevention and control in fishery waters. The established method was applied to analyze water samples from 70 monitoring sites covering 10 fishery waters in Zhejiang Province. A total of 13 drugs were detected, among which amantadine, diazepam, and sulfachloropyridazine showed the three highest detection frequencies. Amantadine was detected in 98.6% of the 70 water samples. A targeted ecological risk assessment was further conducted for amantadine. The ecological risk assessment indicated that amantadine posed ecological risk in some fishery waters. The environments surrounding the sampled fishery waters were analyzed. The occurrence levels of amantadine in fishery waters were closely associated with anthropogenic activities, urban domestic sewage discharge, and agricultural and aquaculture production. More attention should be paid to investigating the migration and transformation behaviors of amantadine in water bodies and assessing its ecological and health impacts. Long-term monitoring and source apportionment of amantadine residues should be strengthened in fishery waters.

Key words: ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）, fishery waters, antibiotics, antiviral drugs, ecological risk