Simultaneous quantification of cyclosporin, tacrolimus, sirolimus and everolimus in whole blood by UHPLC-MS/MS for therapeutic drug monitoring.

Autor: Antunes NJ; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil.; Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.; Analytical Services International (ASI) Ltd, St George's-University of London, London, UK., Kipper K; Analytical Services International (ASI) Ltd, St George's-University of London, London, UK.; Institute of Chemistry, University of Tartu, Tartu, Estonia., Couchman L; Analytical Services International (ASI) Ltd, St George's-University of London, London, UK.; Pharmaceutical Sciences Clinical Academic Group, King's College London, London, UK., Duncan MA; Analytical Services International (ASI) Ltd, St George's-University of London, London, UK., Holt DW; Analytical Services International (ASI) Ltd, St George's-University of London, London, UK., De Nucci G; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil., Johnston A; Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.; Analytical Services International (ASI) Ltd, St George's-University of London, London, UK.
Jazyk: angličtina
Zdroj: Biomedical chromatography : BMC [Biomed Chromatogr] 2021 Jun; Vol. 35 (6), pp. e5071. Date of Electronic Publication: 2021 Feb 02.
DOI: 10.1002/bmc.5071
Abstrakt: The aim of this study was to develop and validate a UHPLC-MS/MS assay to quantify cyclosporin (CYC), tacrolimus (TAC), sirolimus (SIR) and everolimus (EVE) in human whole blood for therapeutic drug monitoring. Analytes were extracted from 50 μL human whole blood by protein precipitation. The separation of the drugs was performed on an Acquity UPLC BEH C18 column. Analytes were eluted with a mobile phase consisting of 2 mM ammonium acetate with 0.1% formic acid (v/v) in deionised water and 2 mM ammonium acetate with 0.1% formic acid (v/v) in methanol at a flow rate of 300 μL/min in gradient elution. The method performance was evaluated by analysing patient blood samples and/or external quality control samples [proficiency testing (PT) scheme]. The method was linear from 23.75 to 1094.0, 1.3 to 42.4, 1.3 to 47.0 and 1.2-41.6 μg/mL for CYC, TAC, SIR and EVE, respectively. The within- and between-assay reproducibility results were ˂ 11%. Results from PT and patient sample quantification were comparable to those obtained previously by an in-house validated method using protein precipitation and liquid-liquid extraction. This method showed good analytical performance for quantifying CYC, TAC, SIR and EVE in whole blood over their respective calibration ranges.
(© 2021 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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