Abstract: A method of liquid chromatography-tandem mass spectrometry was developed for the determination of trace methaqualone(MTQ) residues in culture fish samples. The samples were extracted by n-hexane， purified on Silica column， eluted by V (ethyl ether)∶V (hexan)=1∶1 and separated by liquid chromatography on C₁₈ column with mobile phase of 0.1% formic acid in methanol. MTQ-D₇ was used as internal standard, the quantification was performed with internal standard method. An ion pair of m/z 251.1/91.2 was used for the quantitative analysis of MTQ by MS. The limit of determination is 0.2 μg/kg（S/N≥10）. Spike recoveries of four concentration levels (0.2, 0.5, 1.0 and 20 μg/kg) are in the range of 86.6%—95.9% with relative standard deviation of 2.26%—7.48%.