Clinical Utility of a New Enzymatic Assay for Determination of Mycophenolic Acid in Comparison With an Optimized LC-MS/MS Method

Teun Gelder, I Domke, J Engelmayer, H de Fijter, D Kuypers, K Budde, R Koeger, H Luthe, M Oellerich

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Abstract

The goal of this study was to investigate the clinical utility of a new enzymatic assay for use on COBAS INTEGRA systems (Roche Total MPA assay). From 134 patients, plasma mycophenolic acid (MPA) concentrations were measured with both the enzymatic method and a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) procedure, to compare these assays. The test principle of the enzymatic assay is inhibition of inosine monophosphate dehydrogenase. Method comparison studies revealed good agreement of results (r > 0.99), overall and in patients with delayed graft function or hypoalbuminemia. MPA area under the concentration-time curve (AUCs) obtained with LC-MS/MS (x) and the enzymatic method (v) compared excellent in patients on cyclosporine (y = 1.04x - 1.05, r = 0.992) or tacrolimus (y = 1.02x - 0.63, r = 0.987). MPA exposure determined with either method at different time points after transplantation agreed well (eg, 25th/50th/75th percentile of day 10 AUCs-LC-MS/MS: 25.8/33.8/45.2 versus enzymatic assay: 26.2/34.4/45.3 mg.h/L). AUCs calculated for both methods were lower at the first 3 time points in patients on cyclosporine compared with tacrolimus (week 4 median cyclosporine/tacrolimus: LC-MS/MS 39.6/56.4 versus enzymatic assay 40.5/56.0 mg.h/L). Both LC-MS/MS and the enzymatic methods revealed a tendency toward lower AUCs and predose levels in patients with biopsy-proven acute rejection (BPAR) (day 10 median: 0.9 mg/L with BPAR and 1.7 mg/L without BPAR). The Roche Total MPA assay is a reliable alternative to LC-MS/MS. It can be applied in the clinical setting allowing for easy, fast, and optimized patient management.
Original languageUndefined/Unknown
Pages (from-to)218-223
Number of pages6
JournalTherapeutic Drug Monitoring
Volume31
Issue number2
DOIs
Publication statusPublished - 2009

Research programs

  • EMC MM-04-39-05
  • EMC OR-01-34-01

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