Determination of Cefalothin and Cefazolin in Human Plasma, Urine and Peritoneal Dialysate by UHPLC-MS/MS: application to a pilot pharmacokinetic study in humans
Corresponding Author
Suzanne L. Parker
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia
Correspondence to: S. L. Parker, F Floor, Block 6, School of Medicine, The University of Queensland, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia. Email: [email protected]Search for more papers by this authorYarmarly C. Guerra Valero
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia
Search for more papers by this authorDarren M. Roberts
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia
Search for more papers by this authorJeffrey Lipman
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
Search for more papers by this authorJason A. Roberts
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia
Department of Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Australia
Search for more papers by this authorSteven C. Wallis
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia
Search for more papers by this authorCorresponding Author
Suzanne L. Parker
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia
Correspondence to: S. L. Parker, F Floor, Block 6, School of Medicine, The University of Queensland, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia. Email: [email protected]Search for more papers by this authorYarmarly C. Guerra Valero
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia
Search for more papers by this authorDarren M. Roberts
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia
Search for more papers by this authorJeffrey Lipman
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
Search for more papers by this authorJason A. Roberts
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia
Department of Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Australia
Search for more papers by this authorSteven C. Wallis
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia
Search for more papers by this authorAbstract
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.
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