Abstract: A method for determination of 100 kinds of veterinary drugs by matrix solid-phase dispersive extraction-isotope dilution-liquid chromatographyquadrupole/electrostatic field orbitrap mass spectrometry method was established. 100 kinds of veterinary drug and metabolism residuals were extracted by acetonitrile and cleaned up by C18, separated by Boxton C18（100 mm×2.1 mm, 3.5 μm）column. Acetonitrile (contain 0.1% formic acid) and 0.1% formic acid aqueous were used as the mobile phases for positive mode, acetonitrile and 0.5 mmol/L ammonium fluoride were used as the mobile phases for negative mode, by gradient elution program respectively. Qualitative and quantitative analysis of the target compounds were performed in the full scan and secondary mass spectrometry scan （dd-MS²）modes with positive and negative ionization, and the target compounds were quantified by internal standard method. The target compounds showed good linear relationships in their respective ranges, with correlation coefficients （R²） greater than 0.99. The LOQ of target compounds were in the range of 0.1~10 μg/kg, The average recoveries were between 70%~120% and the relative standard deviations （RSDs） were <25%.