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An ultra performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method has been developed for the simultaneous determination of four beta-lactam antibiotics (amoxicillin, ampicillin, cefotaxime, and cefoperazone) and two P-lactamase inhibitors (tazobactam, sulbactam) in bovine milk. The analytes were extracted with water from bovine milk and purified with Oasis HLB solid phase extraction (SPE) cartridges. The analytes were determined in less than 3 min by UPLC-MS/MS in positive and negative electrospray ionization (ESI) modes, separately. The method was linear over the range of 1-100 mu g/L for tazobactam, sulbactam, ampicillin, and cefoperazone, and 2-100 mu g/L for amoxicillin and cefotaxime. The recoveries for all six analytes in bovine milk ranged from 82.5 to 98.3%. The limits of detection and the limits of quantitation were 0.1-0.2 mu g/L and 0.3-0.5 mu g/L, respectively. The intra- and inter-day precisions were less than 6% for each compound. (C) 2013 Elsevier B.V. All rights reserved.