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

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