Sensitive high-performance liquid chromatography–tandem mass spectrometry method for quantitative analysis of mycophenolic acid and its glucuronide metabolites in human plasma and urine

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2007-10, Vol.858 (1), p.159-167
• Main Authors: Benoit-Biancamano, Marie-Odile, Caron, Patrick, Lévesque, Éric, Delage, Robert, Couture, Félix, Guillemette, Chantal
• Format: Article
• Language: English
• Subjects: AcMPAG; Analysis; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Fundamental and applied biological sciences. Psychology; General pharmacology; Glucuronide; Glucuronides - blood; Glucuronides - metabolism; Glucuronides - urine; HPLC; Humans; Mass spectrometry; Medical sciences; MPAG; Mycophenolic acid; Mycophenolic Acid - blood; Mycophenolic Acid - metabolism; Mycophenolic Acid - urine; Pharmacology. Drug treatments; Reproducibility of Results; Solid Phase Extraction; Tandem Mass Spectrometry - methods
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2007.08.023

A method to determine total and free mycophenolic acid (MPA) and its metabolites, the phenolic (MPAG) and acyl (AcMPAG) glucuronides, using HPLC and mass spectrometry was developed. Mean recoveries in plasma and urine samples were >85%, and the lower limits of quantification for MPA, MPAG and AcMPAG were 0.05, 0.05 and 0.01 mg/L, respectively. For plasma, the assay was linear over 0.05–50 mg/L for MPA and MPAG, and from 0.01 to 10 mg/L for AcMPAG. A validation study demonstrated good inter- and intra-day precision (CV ≤ 11%) and accuracy (bias ≤ 16%) and satisfactory specificity and stability. Pharmacokinetic parameters were assessed in plasma and urine from healthy volunteers after an oral dose of mycophenolate mofetil.