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

Autor(es)

Antunes, Natalicia J. ^{[1, 2, 3]} ; Kipper, Karin ^{[4, 3]} ; Couchman, Lewis ^{[5, 3]} ; Duncan, Marie-Anne ^[3] ; Holt, David W. ^[3] ; De Nucci, Gilberto ^[1] ; Johnston, Atholl ^{[2, 3]}

Afiliação do(s) autor(es)

^[1] State Univ Campinas UNICAMP, Fac Med Sci, Dept Pharmacol, Campinas, SP - Brazil

^[2] Queen Mary Univ London, Barts & London Sch Med & Dent, Clin Pharmacol, William Harvey Res Inst, Charterhouse Sq, London EC1M 6BQ - England

^[3] St Georges Univ London, Analyt Serv Int ASI Ltd, London - England

^[4] Univ Tartu, Inst Chem, Tartu - Estonia

^[5] Kings Coll London, Pharmaceut Sci Clin Acad Grp, London - England

• Tipo de documento: Artigo Científico
• Fonte: BIOMEDICAL CHROMATOGRAPHY; v. 35, n. 6 FEB 2021.
• Citações Web of Science: 1

Resumo

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 mu L 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 mu L/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 mu g/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. (AU)

• Processo FAPESP: 16/22506-1 - Metabolismo do dapaconazol
• Beneficiário: Natalícia de Jesus Antunes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado