Quantification of seven β-lactam antibiotics and two β-lactamase inhibitors in human plasma using a validated UPLC-MS/MS method

There is an increasing interest in monitoring plasma concentrations of beta-lactam antibiotics. The objective of this work was to develop and validate a rapid ultra-performance liquid chromatographic method with tandem mass spectrometric detection (UPLC-MS/MS) for simultaneous quantification of amoxicillin, ampicillin, cefuroxime, cefazolin, ceftazidime, meropenem, piperacillin, clavulanic acid and tazobactam. Sample clean-up included protein precipitation with acetonitrile and back-extraction of acetonitrile with dichloromethane. Six deuterated beta-lactam antibiotics were used as internal standards. Chromatographic separation was performed on a Waters ACQUITY UPLC system using a BEH C-18 column (1.7 mu m, 100 mm x 2.1 mm) applying a binary gradient elution of water and acetonitrile both containing 0.1% formic acid. The total run time was 5.5 min. The developed method was validated in terms of precision, accuracy, linearity, matrix effect and recovery. The assay has now been successfully used to determine concentrations of amoxicillin/clavulanic acid, cefuroxime and meropenem in plasma samples from intensive care patients. (C) 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.