Quantification of total and unbound cefuroxime in plasma by ultra-performance liquid chromatography tandem mass spectrometry in a cohort of critically ill patients with hypoalbuminemia and renal failure

Joost J. van Raaij, Noortje J. D. Mabelis, Kimberly N. Shudofsky, Sjoerd D. Meenks, Jos L. M. L. le Noble, Paddy K. C. Janssen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)

Abstract

Background Pharmacokinetic studies of cefuroxime by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) have been limited to measurements of total concentrations. Here, we developed a robust method for quantifying total and unbound cefuroxime concentrations using UPLC-MS/MS and ultrafiltration in critically ill patients with hypoalbuminemia and renal failure. Methods Method validation included accuracy, linearity, precision, repeatability, recovery, and limit of quantification (LOQ). Feasibility of the method was performed on samples obtained from randomly selected intensive care unit (ICU) patients. Total and unbound cefuroxime concentrations were quantified using UPLC-MS/MS. Sampling times were categorized as trough (180-1 min prior to administration), peak (10-30 min after administration), mid (30-360 min after administration), and continuous (sampling during administration). Pharmacokinetic/pharmacodynamic (PK/PD) targets were unbound cefuroxime concentrations above 4 times the minimum inhibitory concentration (32 mg/L). Results Intra-assay and inter-assay precision was

Original languageEnglish
Article number23100
Number of pages7
JournalJournal of Clinical Laboratory Analysis
Volume34
Issue number3
Early online date30 Nov 2019
DOIs
Publication statusPublished - Mar 2020

Keywords

  • cefuroxime
  • hypoalbuminemia
  • intensive care unit
  • therapeutic drug monitoring
  • unbound concentration
  • PROTEIN-BINDING

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