title: Multicenter evaluation of a new inosine monophosphate dehydrogenase inhibition assay for quantification of total mycophenolic acid in plasma.
abstract: The performance characteristics of a new inosine monophosphate dehydrogenase inhibition assay for the quantification of total mycophenolic acid (MPA) in plasma (Roche Diagnostics) were assessed in a multicenter evaluation. Validation data were collected from four institutions. Within-run and total imprecision were acceptable (n = 21 for each of 7 materials, coefficients of variation ranging 0.7-9.6%). The lower limit of quantification was 0.31 mg/L. The assay was linear from 0.31 to 15.0 mg/L. Method comparison with validated high-performance liquid chromatography with ultraviolet light or liquid chromatography tandem mass spectrometry methods showed good agreement (coefficients of correlation 0.974-0.994, slopes 1.01-1.17, intercepts -0.17 to 0.06). There was no difference found between results from different transplant types (cardiac vs. renal) or comedications (cyclosporine vs. tacrolimus). The recovery of samples from a proficiency testing scheme was acceptable. The cross-reactivity of AcMPAG, an in vitro active metabolite of MPA, was examined by adding AcMPAG to a pool of patient samples and subsequent quantification. MPA overestimation by AcMPAG cross-reactivity was found to be low (<5%). Thus, this interference is expected to be clinically irrelevant. In conclusion, the Roche Total MPA assay is a promising alternative for MPA quantification where chromatographic methods are not available.
authors.affiliation: Department of Clinical Chemistry, University Hospital Goettingen, Germany. gunnar.brandhorst@med.uni-goettingen.de
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brandhorst
authors.forename: Pierre
authors.initials: P
authors.lastname: Marquet
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.forename: Gerhard
authors.initials: G
authors.lastname: Liebisch
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Coffing
authors.forename: Ingrid
authors.initials: I
authors.lastname: Domke
authors.forename: Frank
authors.initials: F
authors.lastname: Streit
authors.forename: Hilmar
authors.initials: H
authors.lastname: Luthe
authors.forename: Michael
authors.initials: M
authors.lastname: Oellerich
mesh_terms: D000918:Antibody Specificity; D002851:Chromatography, High Pressure Liquid; D003429:Cross Reactions; D016903:Drug Monitoring; D004791:Enzyme Inhibitors / Q000097:blood* / Q000494:pharmacology*; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors* / Q000097:blood*; D007291:Inosine Monophosphate / Q000378:metabolism; D013058:Mass Spectrometry; D009173:Mycophenolic Acid / Q000097:blood*; D009243:NAD / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D004791:Enzyme Inhibitors; D009243:NAD; D007291:Inosine Monophosphate; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid