Validation and Application of an HPLC-UV Method for Routine Therapeutic Drug Monitoring of Cefiderocol

Antibiotics (Basel). 2021 Feb 28;10(3):242. doi: 10.3390/antibiotics10030242.

Abstract

Cefiderocol is a new siderophore cephalosporin approved for the treatment of multidrug resistant bacteria including activity against carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa. As cephalosporins are known for their high pharmacokinetic variability in critically ill patients, cefiderocol therapeutic drug monitoring might become a valuable tool. Therefore, we aimed to develop and validate a simple, rapid, cost-effective high performance liquid chromatography (HPLC) method for the quantification of cefiderocol in serum. Samples were treated for protein precipitation followed by chromatographic separation on a reverse phase column (HPLC C-18) with gradient elution of the mobile phase. Cefiderocol was detected via UV absorption and quantification was performed with the internal standard (metronidazole) method. The calibration range showed linearity from 4 to 160 mg/L. The intra and interday precision was less than 10% with a recovery rate of 81%. The method was successfully used for the analysis of subsequent serum samples of critically ill patients and showed good performance in monitoring serum levels and optimizing antibiotic therapy.

Keywords: ESBL; Enterobacterales; cefiderocol; therapeutic drug monitoring.

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