LC–MS/MS method for quantitation of mycophenolic acid, mycophenolic acid acyl-glucuronide, and 7-O-mycophenolic acid glucuronide in serum

Stephen D. Merrigan, Erik Kish-Trier, Jesse C. Seegmiller, Kamisha L. Johnson-Davis

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Mycophenolic acid (MPA) is the active metabolite of the immunosuppressant drug mycophenolate mofetil (MMF), which is commonly prescribed after organ transplantation in conjunction with other immunosuppressants. MMF therapy is monitored to balance therapeutic efficacy with minimizing adverse effects associated with high serum concentrations. A LC–MS/MS method was developed for the quantification of MPA and two additional metabolites, 7-O-mycophenolic acid glucuronide (MPAG) and mycophenolic acid acyl-glucuronide (AcMPAG), in serum using reverse-phase chromatography and multiple reaction monitoring (MRM) in positive electrospray ionization mode. Analytes were chromatographically resolved and the method was linear from 0.5 to 30.0 µg/ml MPA, 4.7 to 300 µg/ml MPAG, and from 0.5 to 30.0 µg/ml AcMPAG. Calibration curves for all analytes had r ≥ 0.990. Intra- and inter-assay imprecision coefficients of variation (CVs) were ≤6.9% and ≤14.5%, respectively. No ion suppression or interferences were observed. The method compared favorably with an unaffiliated reference laboratory. Retrospective data analyses indicate interpatient differences in drug metabolism.

Original languageEnglish (US)
Pages (from-to)41-48
Number of pages8
JournalClinical Mass Spectrometry
Volume3
DOIs
StatePublished - Jan 2017

Bibliographical note

Publisher Copyright:
© 2017

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

Keywords

  • 7-O-mycophenolic acid glucuronide
  • Immunosuppressant
  • Liquid chromatography
  • Mass spectrometry
  • Mycophenolate mofetil
  • Mycophenolic acid
  • Mycophenolic acid acyl-glucuronide

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