Abstract: A method of LC-MS/MS was applied to determine triphenylmethane,thiazide and their metabolites in fish and shrimp samples. The sample was extracted with a mixture of p-toluenesulfonic acid,ammonium acetate and acetonitrile,defatted with hexane,extracted with dichloromethane,and then purified with MCAX solid phase extraction column. Waters BEH C18 column was used as stationary phase and the mixture of 0.15% formic acid solution (with 5 mmol·L-1 ammonium acetate) and acetonitrile was used as mobile phase for gradient elution. ESI+ and MRM were adopted in MS/MS. The linearity ranges of the compounds were found within 20.0 μg·L-1,with limits of quantification (10S/N) of 0.5 μg·kg-1. Recovery rate measured by standard addition method was in the range of 62.6%-108% with RSD′s (n=6) in the range of 2.0%-14%. The method was used to analyze of fish and shrimp samples,giving results consistent with those obtained by the standard method.