title: Determination of Cefalothin and Cefazolin in Human Plasma, Urine and Peritoneal Dialysate by UHPLC-MS/MS: application to a pilot pharmacokinetic study in humans.
abstract: An ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the analysis of cefazolin and cefalothin in human plasma (total and unbound), urine and peritoneal dialysate has been developed and validated. Total plasma concentrations are measured following protein precipitation and are suitable for the concentration range of 1-500 µg/mL. Unbound concentrations are measured from ultra-filtered plasma acquired using Centrifree(®) devices and are suitable for the concentration range of 0.1-500 µg/mL for cefazolin and 1-500 µg/mL for cefalothin. The urine method is suitable for a concentration range of 0.1-20 mg/mL for cefazolin and 0.2-20 mg/mL for cefalothin. Peritoneal dialysate concentrations are measured using direct injection, and are suitable for the concentration range of 0.2-100 µg/mL for both cefazolin and cefalothin. The cefazolin and cefalothin plasma (total and unbound), urine and peritoneal dialysate results are reported for recovery, inter-assay precision and accuracy, and the lower limit of quantification, linearity, stability and matrix effects, with all results meeting acceptance criteria. The method was used successfully in a pilot pharmacokinetic study with patients with peritoneal dialysis-associated peritonitis, receiving either intraperitoneal cefazolin or cefalothin. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Parker
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.
authors.forename: Yarmarly C
authors.initials: YC
authors.lastname: Guerra Valero
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.
authors.forename: Darren M
authors.initials: DM
authors.lastname: Roberts
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.|Department of Intensive Care, Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.|Department of Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Wallis
mesh_terms: D002437:Cefazolin / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002512:Cephalothin / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D010530:Peritoneal Dialysis; D010865:Pilot Projects; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002437:Cefazolin; D002512:Cephalothin
keywords: UHPLC-MS/MS; b-lactam antibiotics; bio-analysis; protein binding