A multi residue analytical method by liquid chromatography-high resolution mass spectrometry was developed for the simultaneous detection of gymnodimine(GYM),spirolides(SPX1),okadaic-acid(OA-C),pectenotoxins(PTX 2),chloroamphenicol,florfenicol and 14 sulfonamides in shellfish tissues.The samples were extracted with methanol,defatted with n-hexane,and back-extracted with ethyl acetate and purified by votexing with ODS.The extract was separated on an Agilent ZORBAX SB-C18 column(3.0 mm×100 mm,1.8 μm) and detected with high resolution mass spectrometry.The results showed that high correlation coefficients(r2＞0.99) of the anaytes were obtained within their respective linear ranges.The limits of quantitation(LOQ) of 4 shellfish biotoxins(SPX1,OA-C,GYM and PTX 2) were 0.1,2.0,0.5，0.5 μg/kg,respectively.The average recoveries for low,intermediate,and high spiked levels ranged from 70.1% to 105.8% with RSDs of 10.1%-14.8%．The proposed method was accurate,rapid and reliable,and could be applied in the qualitative and quantitative analysis of shellfish biotoxins and other toxic substances in shellfish.