Liquid Chromatography-Tandem Mass Spectrometry Method for Therapeutic Drug Monitoring of Dalbavancin in Plasma of Pediatric and Young Adult Patients.


Journal

Therapeutic drug monitoring
ISSN: 1536-3694
Titre abrégé: Ther Drug Monit
Pays: United States
ID NLM: 7909660

Informations de publication

Date de publication:
10 Oct 2024
Historique:
received: 02 03 2024
accepted: 20 07 2024
medline: 23 10 2024
pubmed: 23 10 2024
entrez: 22 10 2024
Statut: aheadofprint

Résumé

Dalbavancin, an antimicrobial lipoglycopeptide, is authorized in Europe for treating acute bacterial infections of the skin and skin structures in adults and pediatric patients aged 3 months and older. However, off-label dosing regimens have been proposed for various indications beyond acute bacterial infections of the skin and skin structures. This study presents a novel bioanalytical method using liquid chromatography-tandem mass spectrometry to quantify dalbavancin in low-volume plasma samples (50 μL). The method underwent validation in accordance with international guidelines for bioanalytical method validation and was applied to 9 clinical samples obtained from pediatric and young adult patients undergoing dalbavancin therapy. Liquid chromatography-tandem mass spectrometry analyses were conducted at the G. Gaslini Institute in Genoa, Italy, utilizing an Ultimate 3000 ultra high performance liquid chromatography system coupled to a TSQ Quantiva Triple Quadrupole system (Thermo Fisher Scientific, Milan, Italy). The analytical procedure involved the addition of deuterated dalbavancin as internal standard and a rapid extraction from 50 µL of human plasma, followed by chromatographic separation on a Thermo Scientific Accucore Polar Premium column. Accurate quantification of the analyte was achieved through multiple reaction monitoring detection. The assay exhibited linearity within the concentration range of 0.66-400 mcg/mL in plasma, demonstrating accuracy and reproducibility in the absence of matrix effects. Stability testing was conducted on both quality controls and real samples to establish a robust protocol under real-life conditions. This fast and reliable dalbavancin quantitation method could improve current pediatric clinical practice by enabling data collection for future dose recommendations in special patient populations.

Sections du résumé

BACKGROUND BACKGROUND
Dalbavancin, an antimicrobial lipoglycopeptide, is authorized in Europe for treating acute bacterial infections of the skin and skin structures in adults and pediatric patients aged 3 months and older. However, off-label dosing regimens have been proposed for various indications beyond acute bacterial infections of the skin and skin structures. This study presents a novel bioanalytical method using liquid chromatography-tandem mass spectrometry to quantify dalbavancin in low-volume plasma samples (50 μL).
METHODS METHODS
The method underwent validation in accordance with international guidelines for bioanalytical method validation and was applied to 9 clinical samples obtained from pediatric and young adult patients undergoing dalbavancin therapy. Liquid chromatography-tandem mass spectrometry analyses were conducted at the G. Gaslini Institute in Genoa, Italy, utilizing an Ultimate 3000 ultra high performance liquid chromatography system coupled to a TSQ Quantiva Triple Quadrupole system (Thermo Fisher Scientific, Milan, Italy). The analytical procedure involved the addition of deuterated dalbavancin as internal standard and a rapid extraction from 50 µL of human plasma, followed by chromatographic separation on a Thermo Scientific Accucore Polar Premium column. Accurate quantification of the analyte was achieved through multiple reaction monitoring detection.
RESULTS RESULTS
The assay exhibited linearity within the concentration range of 0.66-400 mcg/mL in plasma, demonstrating accuracy and reproducibility in the absence of matrix effects. Stability testing was conducted on both quality controls and real samples to establish a robust protocol under real-life conditions.
CONCLUSIONS CONCLUSIONS
This fast and reliable dalbavancin quantitation method could improve current pediatric clinical practice by enabling data collection for future dose recommendations in special patient populations.

Identifiants

pubmed: 39437539
doi: 10.1097/FTD.0000000000001260
pii: 00007691-990000000-00271
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Déclaration de conflit d'intérêts

The authors declare no conflict of interest.

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Auteurs

Alessia Cafaro (A)

Chromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Marcello Mariani (M)

Pediatric Infectious Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Federica Pigliasco (F)

Chromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Giammarco Baiardi (G)

Pharmacology and Toxicology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Clinical Pharmacology Unit, EO Ospedali Galliera, Genoa, Italy; and.

Sebastiano Barco (S)

Chromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Margherita Biondi (M)

Chromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Alessio Mesini (A)

Pediatric Infectious Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Chiara Russo (C)

Division of Infectious Diseases, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.

Carolina Saffioti (C)

Pediatric Infectious Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Francesca Mattioli (F)

Pharmacology and Toxicology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Clinical Pharmacology Unit, EO Ospedali Galliera, Genoa, Italy; and.

Elio Castagnola (E)

Pediatric Infectious Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Giuliana Cangemi (G)

Chromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Classifications MeSH