Fast and Sensitive Analysis of Cefiderocol in Human Plasma Microsamples by Liquid Chromatography-Isotope Dilution Tandem Mass Spectrometry for Therapeutic Drug Monitoring.

Content Provider	Europe PMC
Author	Barone, Rossella Conti, Matteo Cojutti, Pier Giorgio Gatti, Milo Viale, Pierluigi Pea, Federico
Copyright Year	2023
Abstract	Cefiderocol (C) is a parenteral siderophore cephalosporin with relevant inter-individual pharmacokinetic variability among critically ill patients, which may potentially affect effective drug exposure. Therapeutic drug monitoring (TDM) may concur in improving the real-time management of C therapy in clinics. In this study, we developed and validated a fast and sensitive Liquid Chromatography-Isotope Dilution Tandem Mass Spectrometry (LC-ITD-MS/MS) method for measuring C in human plasma microsamples, as small as 3 microliters. Analysis was preceded by a user-friendly pre-analytical single-step and was performed by means of a very fast chromatographic run of 4 min, followed by positive electrospray ionization and detection on a high sensitivity triple quadrupole tandem mass spectrometer operated in multiple reaction monitoring mode. The straightforward analytical procedure was successfully validated, based on the European Medicines Agency (EMA) guidelines, in terms of specificity, sensitivity, linearity, precision, accuracy, matrix effect, extraction recovery, limit of quantification, and stability. The novel method was successfully applied to TDM of C in more than 50 cases of critically carbapenem-resistant Gram-negative bacterial infections and enabled us to optimize antibiotic therapy.
Journal	Antibiotics (Basel, Switzerland)
Volume Number	12
PubMed Central reference number	PMC9952754
Issue Number	2
PubMed reference number	36830124
e-ISSN	20796382
DOI	10.3390/antibiotics12020213
Language	English
Publisher	MDPI
Publisher Date	2023-01-19
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors.
Subject Keyword	cefiderocol therapeutic drug monitoring plasma microsamples Liquid Chromatography-Isotope Dilution Tandem Mass Spectrometry
Content Type	Text
Resource Type	Article
Subject	Biochemistry Pharmacology, Toxicology and Pharmaceutics Microbiology Pharmacology (medical) Infectious Diseases Microbiology (medical)