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A simple and sensitive HPLC method for the simultaneous analysis of free MPA and free MPAG was developed. Separation was achieved on a X-Terra RP18 column with acetonitrile–40 mM orthophosphoric acid as eluents using a gradient elution mode over 35 min at a flow rate of 1.5 ml/min. The assay was linear in the range 0.005 mg/L (LOQ) to 5 mg/L for free MPA and 0.05 mg/L (LOQ) to 200 mg/L for free MPAG. Isolation of free MPA and free MPAG was done by ultrafiltration and the ultrafiltrate was directly injected. A positive correlation between MPA free fractions and free MPAG concentrations was found. Likewise, free MPAG was related to total MPAG concentrations in the seven heart transplant patients.

The study assessed the removal of mycophenolic acid (MPA) and its major glucuronide metabolite (MPAG) during continuous venovenous hemofiltration (CVVHF) and continuous venovenous hemodiafiltration (CVVHDF) in 4 heart transplant recipients treated for at least 6 days with mycophenolate mofetil (MMF) in addition to cyclosporine and corticosteroids. The sieving coefficient ranged from 0.02 to 0.04 for MPA and from 0.15 to 0.33 for MPAG. The clearance of MPAG by CVVHDF or CVVHF ranged from 7.52 mL/min to 19.45 mL/min, and that of MPA was lower than 2.28 mL/min, with no significant difference between the two continuous replacement therapies. Whereas MPA percentage recovered by hour following CVVHDF or CVVHF was negligible, the percentage of MPAG represents up to 12.9% of the administered dose. A relevant decrease in the free fraction of MPA and MPAG was observed after continuous renal replacement therapy (CRRT). These preliminary results demonstrate that MPAG is able to permeate the filter. In light of the alteration in protein binding following CRRT and the competition between MPA and MPAG to albumin site, drug monitoring of MPA and MPAG in patients undergoing CVVHDF or CVVHF may be suggested. Moreover, monitoring of free MPA may be of interest for these patients.

Drugs in solution may be adsorbed to the surface of containers and thus be removed from solution. We studied the loss of mycophenolic acid (MPA) and its major metabolite mycophenolic acid glucuronide (MPAG) from glass, polystyrene, and polypropylene containers based on solvent and time of contact. MPA was from Hoffmann-La Roche and MPAG from Analytical Services International Ltd. Acetonitrile (Uvasol; purity >99.8%), methanol (Uvasol; purity >99.8%), and orthophosphoric acid (85% Suprapur; Merck) were HPLC grade. The NaCl solution (9 g/L, pH 7.4) was from Fresenius Kabi. Stock solutions of MPA, MPAG, and MPA/MPAG were prepared in acetonitrile–water (80:20 by volume) and stored in polystyrene tubes at −80 °C. The chromatographic analysis was performed as described previously (1), with a minor gradient modification. Studies were performed on ice, which stabilizes drugs for at least 8 h (2). The MPA/MPAG stock solution was diluted with acetonitrile, methanol, or isotonic NaCl in five 6-mL glass (VSM; 69% SiO2, 13% Na2 …