title: Clinical utility of a new enzymatic assay for determination of mycophenolic acid in comparison with an optimized LC-MS/MS method.
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 (y) 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.
authors.affiliation: Department of Hospital Pharmacy, Erasmus Medical Center, Molewaterplein 40, Rotterdam, The Netherlands. t.vangelder@erasmusmc.nl
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
authors.forename: Ingrid
authors.initials: I
authors.lastname: Domke
authors.forename: Jutta
authors.initials: J
authors.lastname: Engelmayer
authors.forename: Hans
authors.initials: H
authors.lastname: de Fijter
authors.forename: Dirk
authors.initials: D
authors.lastname: Kuypers
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
authors.forename: Robin
authors.initials: R
authors.lastname: Koeger
authors.forename: Hilmar
authors.initials: H
authors.lastname: Luthe
authors.forename: Michael
authors.initials: M
authors.lastname: Oellerich
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D019540:Area Under Curve; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007166:Immunosuppressive Agents / Q000097:blood*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000097:blood*; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid