Abstract: OBJECTIVE To approach the determination of the residues of deuterated internal standard in medicinal oyster by LC-MS/MS with deuterated internal standard to improve the safety of medicinal oyster materials. METHODS A mixture of deuterated internal standard was added to the samples, purified by acidic alumina cartridges and then isolated through acidic alumina cartridges. Elute the alumina cartridges with acetonitrile, and the residue was tested by LC-MS/MS, with the gradient of mobile phase composed of acetonitrile and 5 mmol·L^-1 ammonium acetate solution. RESULTS All molecules in samples were in good linear of 0.5-10 μg·kg^-1, with a mean recovery at 90.5%~102.6%, and the instrumental limit of quantitative detection was 0.054 3-0.297 8 μg·kg^-1. CONCLUSION The method is proved to be sensitive and accurate, repeatable and specific with little interference, extremely consultable for inspection for residues of triphenylmethane dyes in medicinal oyster materials.