Abstract:Based on ultra-high-performance liquid chromatography-Orbitrap high-resolution mass spectrometry（UPLC-Orbitrap HRMS）technology，this study developed a solvent for the simultaneous extraction of multiple types of veterinary drug residues in aquatic samples，and established a rapid detection method for 79 types of veterinary drug residues in fish，shrimp，and shellfish.The target compounds in the samples were extracted using a mixed solvent [acetonitrile∶methanol∶water （3∶1∶1，volume ratio）] containing 1% acetic acid and 10 mmol/L ethylenediaminetetraacetic acid disodium salt（EDTA-2Na），followed by purification using a Waters HLB solidphase extraction column.During detection，a Waters BEH C18 chromatographic column was used for separation，with gradient elution using 2 mmol/L ammonium formate aqueous solution （containing 0.01% formic acid）and methanol.MS was performed in positive and negative ion simultaneous full scan/data-dependent secondary scan mode，and the separation and data acquisition of target compounds were completed within 20 min.An HRMS library meeting the experimental requirements was established，and the linear correlation of the 79 target compounds ranged from 0.5 to 200.0 μg/kg with good correlation coefficients （R2＞0.99）.Except for five compounds（cefazolin，ceftiofur，cefadroxil，piperacillin，and malachite green） with relatively low recovery rates in fish，shrimp，and shellfish samples，the recovery rates for the rest ranged from 50% to 120%，with relative standard deviations of 0.69% to 19.91%.The quantification limits for the 79 drugs ranged from 0.2 to 5.0 μg/kg.This method could be used for the simultaneous rapid screening and determination of 79 veterinary drugs in aquatic products.