Determination of mycophenolic acid and its phenyl glucuronide in human plasma, ultrafiltrate, blood, DBS and dried plasma spots

Background: Analysis of mycophenolic acid (MPA), the active form of the immunosuppressive drug mycophenolate mofetil, and its glucuronide metabolite MPAG is required for therapeutic monitoring and postmarketing clinical studies. Dried blood spots (DBS) and dried plasma spots (DPS) could be alternatives to conventional assays for small-volume sampling and easy shipment. Results: A LC-MS/MS method with online SPE was established using stable isotope labeled analytes as internal standards. The quantitation limits were set at 0.1 and 1 mu g/ml, for total MPA and MPAG, respectively, in plasma, blood, DBS and DPS, but 100-fold lower for free MPA in ultrafiltrate. Ahlstrom 226 or Whatman FTA (R) DMPK-B cards were well suited for DBS and DPS analyses. Conclusion: MPA and MPAG were analyzed in human plasma and blood either as liquid or dried on cards with similar assay quality. Care should be taken to avoid back-conversion of an instable acyl glucuronide metabolite to MPA.