Cargando…

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

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 implementati...

Descripción completa

Detalles Bibliográficos
Autores principales: Barone, Rossella, Conti, Matteo, Giorgi, Beatrice, Gatti, Milo, Cojutti, Pier Giorgio, Viale, Pierluigi, Pea, Federico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135283/
https://www.ncbi.nlm.nih.gov/pubmed/37107082
http://dx.doi.org/10.3390/antibiotics12040719
_version_ 1785031940579000320
author Barone, Rossella
Conti, Matteo
Giorgi, Beatrice
Gatti, Milo
Cojutti, Pier Giorgio
Viale, Pierluigi
Pea, Federico
author_facet Barone, Rossella
Conti, Matteo
Giorgi, Beatrice
Gatti, Milo
Cojutti, Pier Giorgio
Viale, Pierluigi
Pea, Federico
author_sort Barone, Rossella
collection PubMed
description 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.
format Online
Article
Text
id pubmed-10135283
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-101352832023-04-28 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 Barone, Rossella Conti, Matteo Giorgi, Beatrice Gatti, Milo Cojutti, Pier Giorgio Viale, Pierluigi Pea, Federico Antibiotics (Basel) Article 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. MDPI 2023-04-06 /pmc/articles/PMC10135283/ /pubmed/37107082 http://dx.doi.org/10.3390/antibiotics12040719 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Barone, Rossella
Conti, Matteo
Giorgi, Beatrice
Gatti, Milo
Cojutti, Pier Giorgio
Viale, Pierluigi
Pea, Federico
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135283/
https://www.ncbi.nlm.nih.gov/pubmed/37107082
http://dx.doi.org/10.3390/antibiotics12040719
work_keys_str_mv AT baronerossella fastandsensitivemethodforsimultaneousquantificationofmeropenemandvaborbactaminhumanplasmamicrosamplesbyliquidchromatographytandemmassspectrometryfortherapeuticdrugmonitoring
AT contimatteo fastandsensitivemethodforsimultaneousquantificationofmeropenemandvaborbactaminhumanplasmamicrosamplesbyliquidchromatographytandemmassspectrometryfortherapeuticdrugmonitoring
AT giorgibeatrice fastandsensitivemethodforsimultaneousquantificationofmeropenemandvaborbactaminhumanplasmamicrosamplesbyliquidchromatographytandemmassspectrometryfortherapeuticdrugmonitoring
AT gattimilo fastandsensitivemethodforsimultaneousquantificationofmeropenemandvaborbactaminhumanplasmamicrosamplesbyliquidchromatographytandemmassspectrometryfortherapeuticdrugmonitoring
AT cojuttipiergiorgio fastandsensitivemethodforsimultaneousquantificationofmeropenemandvaborbactaminhumanplasmamicrosamplesbyliquidchromatographytandemmassspectrometryfortherapeuticdrugmonitoring
AT vialepierluigi fastandsensitivemethodforsimultaneousquantificationofmeropenemandvaborbactaminhumanplasmamicrosamplesbyliquidchromatographytandemmassspectrometryfortherapeuticdrugmonitoring
AT peafederico fastandsensitivemethodforsimultaneousquantificationofmeropenemandvaborbactaminhumanplasmamicrosamplesbyliquidchromatographytandemmassspectrometryfortherapeuticdrugmonitoring