Portal de Periódicos da CAPES

HPLC‐UV assay for monitoring total and unbound mycophenolic acid concentrations in children

2008; Wiley; Volume: 23; Issue: 1 Linguagem: Inglês

10.1002/bmc.1088

1099-0801

Lihua Zeng, Christa E. Nath, Peter J. Shaw, John Earl, Andrew J. McLachlan,

Biochemical and Molecular Research

Abstract A simple, accurate and sensitive HPLC method was developed for measuring total and unbound mycophenolic acid (MPA) in human plasma. Total MPA was extracted by protein precipitation and ultrafiltration was used to assess unbound MPA concentrations. The supernatant (20 µL) or ultrafiltrate (100 µL) was injected onto a C 18 HPLC column with a mobile phase of 0.05 m sodium phosphate buffer (pH 2.31)–acetonitrile (55:45, v/v for total MPA; 50:50 for unbound MPA) with UV detection at 254 nm. The extraction recovery was over 93% and reproducible. The assay was linear over the concentration range of 0.07–50 mg/L for total MPA and 4–1500 µg/L for unbound MPA. Intra‐ and inter‐day assay reproducibility was less than 10%. Detection limits were 0.04 mg/L and 2 µg/L for total and unbound MPA, respectively. The assay utility was established in samples collected from five paediatric bone marrow transplant recipients who were receiving intravenous doses of mycophenolate mofetil. In these patients MPA concentrations ranged from 0.07 to 7.83 mg/L and unbound drug concentrations ranged from 2.1 to 107.5 µg/L. This method can be effectively applied to MPA pharmacokinetics in paediatric patients. Copyright © 2008 John Wiley & Sons, Ltd.