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

• Main Authors: Julia Zimmer (Author), Anka C. Röhr (Author), Stefan Kluge (Author), Jonas Faller (Author), Otto R. Frey (Author), Dominic Wichmann (Author), Christina König (Author)
• Format: Book
• Published: MDPI AG, 2021-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antibiotics10030242; 2079-6382
• Keywords: ESBL; Enterobacterales; cefiderocol; therapeutic drug monitoring; Therapeutics. Pharmacology; RM1-950
• Source: Antibiotics, Vol 10, Iss 3, p 242 (2021)

Cefiderocol is a new siderophore cephalosporin approved for the treatment of multidrug resistant bacteria including activity against carbapenem-resistant Enterobacterales and <i>Pseudomonas aeruginosa</i>. 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.