Development of a CE method for the determination of mycophenolic acid in human plasma: a comparison with HPLC.
Mycophenolate mofetil (MMF) is a widely used drug for the maintenance of immunosuppressive therapy in renal-transplant recipients. MMF is rapidly metabolized in vivo to mycophenolic acid (MPA), a reversible, noncompetitive inhibitor of inosine monophosphate dehydrogenase, which represents a limiting enzyme in lymphocyte proliferation. MPA shows large interindividual pharmacokinetic variability: its monitoring is therefore of primary importance to achieve adequate immunosuppression with minimized risk of graft rejection or toxicity. We developed a CE method for the determination of total MPA (tMPA) in plasma, based on easy sample preparation; CE evaluation of tMPA was performed in 30 mmol/L sodium-borate with 10 mmol/L SDS (pH 10.00) at 25 degrees C using a 60 cm (54.5 to window) uncoated capillary with UV detection at 254 nm wavelength. MPA was readily detectable in plasma; the CE method was linear in the range of 0.7-120 microg/mL (r >0.992). Intra- and interassay imprecision was <7% except for the lowest spiked MPA concentration, which had an intra-assay RSD% of 14.7 compared to 18.3 interassay. Data by CE were compared with results obtained by a validated HPLC method. CE assay of tMPA exhibited a very good correlation (r(2) >0.988) with respect to HPLC; Bland-Altman difference versus average showed a mean of -0.18 microg/mL +/- 1.14 SD. CE determination of tMPA is a robust, sensitive and reproducible method with the advantage over HPLC of being fast, simple and unexpensive, also enabling quick assessment of MPA for pharmacokinetic studies.
Carlucci
Filippo
F
Dipartimento di Medicina Interna, Scienze Endocrino-Metaboliche e Biochimica, University of Siena, Siena, Italy. carlucci@unisi.it
Anzini
Maurizio
M
Rovini
Michele
M
Cattaneo
Dario
D
Merlini
Simona
S
Tabucchi
Antonella
A
D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016572:Cyclosporine / Q000737:chemistry*; D016903:Drug Monitoring / Q000379:methods*; D019075:Electrophoresis, Capillary / Q000379:methods*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D015394:Molecular Structure; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013048:Specimen Handling
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid