Abstract: HPLC-MS/MS was applied to measure melamine residue in milk. The sample was extracted with acetonitrile-water,purified by Waters Oasis MCX solid phase extraction column,dried by nitrogen at 50 ℃,dissolved with 1 mL of acetonitrile and used for HPLC-MS/MS analysis. Waters Hilic column (100 mm×2.1 mm,3 μm) was used as stationary phase,and a mixture (95+5) of acetonitrile and 5 mmol·L-1 of ammonium acetate as mobile phase. ESI+ and MRM were adopted in MS/MS. Internal standard method was used for quantization. Linearity range of melamine was within 10.0 μg·L-1,the detection limit (3S/N) was 0.5 μg·kg-1. Tests for recovery and precision were made by addition of melamine,giving values of recovery in the range of 99.8%-103% and values of RSD′s (n=10) in the range of 1.9%-3.2%.