title: Development and validation of a fast and uniform approach to quantify β-lactam antibiotics in human plasma by solid phase extraction-liquid chromatography-electrospray-tandem mass spectrometry.
abstract: Monitoring of plasma antibiotic concentrations is necessary for individualization of antimicrobial chemotherapy dosing in special patient populations. One of these special populations of interest are the post-bariatric surgery patients. Until today, little is known on the effect of this procedure on drug disposition and efficacy. Therefore, close monitoring of antimicrobial plasma concentrations in these patients is warranted. A fast and uniform ultra-high-performance liquid chromatography (UPLC) method with tandem mass spectrometric detection (MS/MS) has been developed and qualified for the simultaneous quantification of β-lactam antibiotics in human plasma. Compounds included in this multi-component analysis are: amoxicillin, ampicillin, phenoxymethylpenicillin, piperacillin, cefuroxime, cefadroxil, flucloxacillin, meropenem, cefepime, ceftazidime, tazobactam, linezolid and cefazolin. After spiking of five different stable isotope labelled internal standards, plasma samples were prepared for UPLC-MS/MS analysis by mixed-mode solid phase extraction. The developed method was proven to be free of (relative) matrix effects and proved to be reliable for the quantification of 12 out of 13 β-lactam antibiotics. As a proof of concept the method has been applied to plasma samples obtained from a healthy volunteer treated with amoxicillin. The analytical method is suitable for use in a therapeutic drug monitoring setting, providing the clinician with reliable measurements on β-lactam antibiotic plasma concentrations in a timely manner.
authors.affiliation: Laboratory of Medical Biochemistry and Clinical Analysis, Ghent University, Harelbekestraat 72, 9000 Gent, Belgium. Pieter.colin@ugent.be
authors.forename: Pieter
authors.initials: P
authors.lastname: Colin
authors.forename: Lies
authors.initials: L
authors.lastname: De Bock
authors.forename: Huybrecht
authors.initials: H
authors.lastname: T'jollyn
authors.forename: Koen
authors.initials: K
authors.lastname: Boussery
authors.forename: Jan
authors.initials: J
authors.lastname: Van Bocxlaer
mesh_terms: D000900:Anti-Bacterial Agents / Q000097:blood* / Q000737:chemistry; D002853:Chromatography, Liquid; D016903:Drug Monitoring; D006801:Humans; D052616:Solid Phase Extraction; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D054928:Validation Studies as Topic; D047090:beta-Lactams / Q000097:blood* / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams