A liquid chromatography-tandem mass spectrometry platform for the routine therapeutic drug monitoring of 14 antibiotics: Application to critically ill pediatric patients.
Antibiotics
Liquid chromatography-tandem mass spectrometry
Pediatric
Therapeutic drug monitoring
Journal
Journal of pharmaceutical and biomedical analysis
ISSN: 1873-264X
Titre abrégé: J Pharm Biomed Anal
Pays: England
ID NLM: 8309336
Informations de publication
Date de publication:
15 Jul 2020
15 Jul 2020
Historique:
received:
08
01
2020
revised:
17
03
2020
accepted:
20
03
2020
pubmed:
7
4
2020
medline:
30
3
2021
entrez:
7
4
2020
Statut:
ppublish
Résumé
The accurate measurement of plasma levels of antibiotics is crucial for the individualization of antimicrobial therapies based on PK/PD strategies. In this paper we describe a new rapid and simple LC-MS/MS platform for quantifying 14 antibiotics (amikacin, amoxicillin, ceftazidime, ciprofloxacin, colistin, daptomycin, gentamicin, linezolid, meropenem, piperacillin, teicoplanin, tigecycline, tobramycin and vancomycin) and a beta-lactamase inhibitor (tazobactam) starting from 50 μL plasma samples. Analyses were performed on a Thermo Scientific™ Ultimate™ 3000 LC system (Thermo Fisher Scientific, Milan, Italy) coupled to a Thermo Scientific™ TSQ Quantiva™ Triple Quadrupole mass spectrometer. After fast protein precipitation protocols and addition of deuterated internal standards, samples were subjected to a fast HPLC gradient separation and the 15 drugs were quantified using multiple reaction monitoring of specific transitions over a wide range of concentrations. The suitability of the assay for TDM was tested on plasma samples derived from pediatric patients under treatment with one or more antibiotics. The overall turnaround time of the assay was 20 min. The assay was validated following EMA guidelines for bioanalytical method validation and showed excellent accuracy (ranging from 85.3 and 112.7) and reproducibility (ranging from 1.3 to 9.7) as well as the absence of matrix effects (<15 %) for all the drugs tested. The lower limits of quantifications were between 0.1 and 2 mg/L. the recovery rate exceeded 85 % for all the drug tested. Stability was evaluated in different conditions thus allowing the setting up of reliable operative procedures. This work provides a LC-MS/MS platform validated for clinical use for a rapid quantification of a broad spectrum of drugs having different chemical characteristics in a small volume of plasma and is suitable for real-time TDM-guided personalization of antimicrobial treatment in critically ill patients.
Sections du résumé
BACKGROUND
BACKGROUND
The accurate measurement of plasma levels of antibiotics is crucial for the individualization of antimicrobial therapies based on PK/PD strategies. In this paper we describe a new rapid and simple LC-MS/MS platform for quantifying 14 antibiotics (amikacin, amoxicillin, ceftazidime, ciprofloxacin, colistin, daptomycin, gentamicin, linezolid, meropenem, piperacillin, teicoplanin, tigecycline, tobramycin and vancomycin) and a beta-lactamase inhibitor (tazobactam) starting from 50 μL plasma samples.
METHODS
METHODS
Analyses were performed on a Thermo Scientific™ Ultimate™ 3000 LC system (Thermo Fisher Scientific, Milan, Italy) coupled to a Thermo Scientific™ TSQ Quantiva™ Triple Quadrupole mass spectrometer. After fast protein precipitation protocols and addition of deuterated internal standards, samples were subjected to a fast HPLC gradient separation and the 15 drugs were quantified using multiple reaction monitoring of specific transitions over a wide range of concentrations. The suitability of the assay for TDM was tested on plasma samples derived from pediatric patients under treatment with one or more antibiotics.
RESULTS
RESULTS
The overall turnaround time of the assay was 20 min. The assay was validated following EMA guidelines for bioanalytical method validation and showed excellent accuracy (ranging from 85.3 and 112.7) and reproducibility (ranging from 1.3 to 9.7) as well as the absence of matrix effects (<15 %) for all the drugs tested. The lower limits of quantifications were between 0.1 and 2 mg/L. the recovery rate exceeded 85 % for all the drug tested. Stability was evaluated in different conditions thus allowing the setting up of reliable operative procedures.
CONCLUSIONS
CONCLUSIONS
This work provides a LC-MS/MS platform validated for clinical use for a rapid quantification of a broad spectrum of drugs having different chemical characteristics in a small volume of plasma and is suitable for real-time TDM-guided personalization of antimicrobial treatment in critically ill patients.
Identifiants
pubmed: 32251979
pii: S0731-7085(20)30066-2
doi: 10.1016/j.jpba.2020.113273
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
113273Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.