title: Quantification of seven β-lactam antibiotics and two β-lactamase inhibitors in human plasma using a validated UPLC-MS/MS method.
abstract: There is an increasing interest in monitoring plasma concentrations of β-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 β-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 μm, 100 mm×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.
authors.affiliation: Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, De Pintelaan 185, Building 2P8, 9000 Ghent, Belgium. Mieke.Carlier@ugent.be
authors.forename: Mieke
authors.initials: M
authors.lastname: Carlier
authors.forename: Veronique
authors.initials: V
authors.lastname: Stove
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.forename: Eric
authors.initials: E
authors.lastname: Van de Velde
authors.forename: Jan J
authors.initials: JJ
authors.lastname: De Waele
authors.forename: Alain G
authors.initials: AG
authors.lastname: Verstraete
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood*; D006805:Human Experimentation; D006801:Humans; D010949:Plasma / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D047090:beta-Lactams / Q000008:administration & dosage / Q000097:blood*
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D047090:beta-Lactams