In order to investigate the pharmacokinetic profiles of cefuroxime lysine, a new second generation cephalosporins, in liver-injured rat model, an ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method for the determination of cefuroxime in liver-injured rat plasma was developed and validated. The plasma sample was pretreated by protein precipitation with acidified acetonitrile. The analytes were separated on a Shim-pack XR-ODS column (75 mm x 3.0 mm, 2.2 microm) with acetonitrile-0. 1% formic acid aqueous solution (40:60, v/v) as the mobile phase at a flow rate of 400 microL/min. The mass spectrometer was operated in multiple reaction monitoring (MRM) mode with a negative electrospray ionization (ESI) interface. The precursor to product ion transitions of m/z 423.2 --> 206.8 and m/z 454.1 --> 238.4 were selected to determine cefuroxime and cefotaxime (internal standard, IS), respectively. The linearities ranged from 0.01 to 1 mg/L and 1 to 400 mg/L (r > 0.99), and the limit of quantification of cefuroxime was 0.01 mg/L. The relative standard deviations (RSDs) of intra- and inter-day precisions were both less than 11.5%, and the accuracy (relative error) was between -7.1% and 2.2%. The mean extraction recovery was more than 83.5%. The total run time was 3.0 min per sample. The method is simple and fast for the preliminary pharmacokinetic study of cefuroxime lysine in liver-injured rats.