Ready for TDM: Simultaneous quantification of amikacin, vancomycin and creatinine in human plasma employing ultra-performance liquid chromatography-tandem mass spectrometry.

Autor: da Silva ACC; Analytical Toxicology Laboratory, Universidade Feevale, Novo Hamburgo, RS, Brazil; Graduate Program on Toxicology and Analytical Toxicology, Universidade Feevale, Novo Hamburgo, RS, Brazil., de Lima Feltraco Lizot L; Analytical Toxicology Laboratory, Universidade Feevale, Novo Hamburgo, RS, Brazil; Graduate Program on Toxicology and Analytical Toxicology, Universidade Feevale, Novo Hamburgo, RS, Brazil., Bastiani MF; Analytical Toxicology Laboratory, Universidade Feevale, Novo Hamburgo, RS, Brazil; Graduate Program on Toxicology and Analytical Toxicology, Universidade Feevale, Novo Hamburgo, RS, Brazil., Antunes MV; Analytical Toxicology Laboratory, Universidade Feevale, Novo Hamburgo, RS, Brazil; Graduate Program on Toxicology and Analytical Toxicology, Universidade Feevale, Novo Hamburgo, RS, Brazil., Brucker N; Graduate Program on Pharmacology, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil., Linden R; Analytical Toxicology Laboratory, Universidade Feevale, Novo Hamburgo, RS, Brazil; Graduate Program on Toxicology and Analytical Toxicology, Universidade Feevale, Novo Hamburgo, RS, Brazil. Electronic address: rafael.linden@feevale.br.
Jazyk: angličtina
Zdroj: Clinical biochemistry [Clin Biochem] 2019 Aug; Vol. 70, pp. 39-45. Date of Electronic Publication: 2019 Jun 20.
DOI: 10.1016/j.clinbiochem.2019.06.011
Abstrakt: Background: Amikacin (AMI) and vancomycin (VAN) are antibiotics largely used in intensive care in the empiric treatment of severe infections by multi-resistant gram-negative and gram-positive bacteria. AMI and VAN are eliminated untransformed by glomerular filtration, showing depuration ratio highly correlated with creatinine (CRE) clearance. AMI, VAN and CRE are highly polar structures, presenting poor retention in reversed-phase liquid chromatography when using conventional stationary phases.
Objective: This study aimed to develop and validate a simple UPLC-MS/MS method for simultaneous determination of AMI, VAN, and CRE in human plasma for therapeutic drug monitoring.
Results: Samples were prepared by protein precipitation, followed by dilution. Heptafluorobutyric acid (HFBA) was added to the mobile phase at low concentration (0.01%), and separation was performed in an ultra-performance reversed-phase column (particle diameter of 1.8 μm). These conditions allowed retention times of 0.92, 0.93, 2.12, 2.17 and 2.27 min for CRE, CRE-D3, AMI, KAN and VAN, respectively. The assay was linear from 0.5 to 100 mg L -1 for AMI and VAN and 5 to 100 mg L -1 . Precision, accuracy and stability assays were acceptable according to bioanalytical validation guidelines. Suitable results. Matrix effects were in the range of +10.5 to +11.6% for AMI, -4.3 to -4.5% for VAN, and - 1.7 to +0.7 for CRE.
Conclusion: The first assay for the simultaneous determination of AMI, VAN and CRE in plasma by liquid chromatography-tandem mass spectrometry was reported. This assay allows the obtention of the necessary analytical data for the clinical application of population pharmacokinetic methods for therapeutic drug monitoring of AMI and VAN.
(Copyright © 2019 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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