Sensitive high-performance liquid chromatography-tandem mass spectrometry method for quantitative analysis of mycophenolic acid and its glucuronide metabolites in human plasma and urine.
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 10mg/L for AcMPAG. A validation study demonstrated good inter- and intra-day precision (CV<or=11%) and accuracy (bias<or=16%) and satisfactory specificity and stability. Pharmacokinetic parameters were assessed in plasma and urine from healthy volunteers after an oral dose of mycophenolate mofetil.
Benoit-Biancamano
Marie-Odile
MO
Canada Research Chair in Pharmacogenomics, Laboratory of Pharmacogenomics, Oncology and Molecular Endocrinology Research Center, CHUL Research Center and Faculty of Pharmacy, Laval University, G1V 4G2 Québec, Canada.
Caron
Patrick
P
Lévesque
Eric
E
Delage
Robert
R
Couture
Félix
F
Guillemette
Chantal
C
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D020719:Glucuronides / Q000097:blood* / Q000378:metabolism / Q000652:urine*; D006801:Humans; D009173:Mycophenolic Acid / Q000097:blood* / Q000378:metabolism / Q000652:urine*; D015203:Reproducibility of Results; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry / Q000379:methods*