Quantification of mycophenolic acid in human plasma by liquid chromatography with time-of-flight mass spectrometry for therapeutic drug monitoring

Author(s)

Antunes, Natalicia J. ^{[1, 2, 3]} ; Ince, Nina ^{[3, 4]} ; Raymond, Jason ^{[3, 4]} ; Kipper, Karin ^{[3, 5]} ; Couchman, Lewis ^{[3, 6]} ; Holt, David W. ^[3] ; De Nucci, Gilberto ^[1] ; Johnston, Atholl ^{[2, 3]}

Affiliation

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

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

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

^[4] Univ Surrey, Dept Chem, Guildford, Surrey - England

^[5] Univ Tartu, Inst Chem, Tartu - Estonia

^[6] Kings Coll London, Pharmaceut Sci Clin Acad Grp, London - England

• Document type: Journal article
• Source: BIOMEDICAL CHROMATOGRAPHY; v. 35, n. 3 NOV 2020.
• Web of Science Citations: 0

Abstract

This study presents, for the first time, the development and validation of a liquid chromatography and time-of-flight mass-spectrometry (LC-TOF-MS) based assay to quantify mycophenolic acid (MPA) in patient samples as part of a routine therapeutic drug monitoring service. MPA was extracted from 50 mu l human plasma by protein precipitation, using sulindac as internal standard (IS). Separation was obtained on a Luna (TM) Omega polar C-18 column kept at 40 degrees C. The mobile phase consisted of a mixture of acetonitrile-deionized water (50:50, v/v) with 0.1% formic acid at a flow rate of 350 mu l/min. Analyte and IS were monitored on a TOF-MS using a Jet-Stream (TM) (electrospray) interface running in positive mode. Assay performance was evaluated by analysing patient plasma (N = 69) and external quality assessment (N = 6) samples. The retention times were 2.66 and 2.18 min for MPA and IS, respectively. The lower limit of quantification of MPA was 0.1 mu g/ml. The within- and between-assay reproducibility results ranged from 1.81 to 10.72%. Patient and external quality assessment sample results were comparable with those obtained previously by an in-house validated LC-MS/MS method. This method showed satisfactory analytical performance for the determination of MPA in plasma over the calibration range of 0.1-15.0 mu g/ml. (AU)

• FAPESP's process: 16/22506-1 - Metabolism of dapaconazole
• Grantee: Natalícia de Jesus Antunes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral