Fast and Sensitive Method for Simultaneous Quantification of Meropenem and Vaborbactam in Human Plasma Microsamples by Liquid Chromatography-Tandem Mass Spectrometry for Therapeutic Drug Monitoring.

Content Provider	Europe PMC
Author	Barone, Rossella Conti, Matteo Giorgi, Beatrice Gatti, Milo Cojutti, Pier Giorgio Viale, Pierluigi Pea, Federico
Editor	Pipitone, Giuseppe Nunnari, Giuseppe Taglietti, Fabrizio
Copyright Year	2023
Abstract	Meropenem (MRP)-Vaborbactam (VBR) is a novel beta-lactam/beta-lactamase inhibitor used for the management of difficult-to-treat Gram-negative infections. Among critically ill patients, MRP-VBR shows remarkable inter-individual variability in pharmacokinetic behavior, thus justifying the implementation of therapeutic drug monitoring (TDM) for improving real-time management in different challenging scenarios. In this study, we developed and validated a fast and sensitive Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) method for the simultaneous quantification of MRP and VBR in human plasma microsamples of 3 microliters. The analysis required only a single-step sample preparation and was performed by means of a 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 modes. The straightforward analytical procedure was successfully validated, based on the EMA guidelines, in terms of specificity, sensitivity, linearity, precision, accuracy, matrix effect, extraction recovery, the limit of quantification, and stability. The novel method was successfully applied for simultaneously measuring MRP and VBR concentrations in more than 42 plasma samples collected from critically ill patients affected by carbapenem-resistant Gram-negative bacteria infections.
Journal	Antibiotics (Basel, Switzerland)
Volume Number	12
PubMed Central reference number	PMC10135283
Issue Number	4
PubMed reference number	37107082
e-ISSN	20796382
DOI	10.3390/antibiotics12040719
Language	English
Publisher	MDPI
Publisher Date	2023-04-06
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	meropenem vaborbactam therapeutic drug monitoring plasma micro samples liquid chromatography–tandem mass spectrometry
Content Type	Text
Resource Type	Article
Subject	Biochemistry Pharmacology, Toxicology and Pharmaceutics Microbiology Pharmacology (medical) Infectious Diseases Microbiology (medical)