Simultaneous quantification of mycophenolic acid and its glucuronide metabolites in human plasma by an UPLC–MS/MS assay

Daping Zhang, Diana S.L. Chow, Jamie Renbarger

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The aim of this study was to develop a reliable UPLC–MS/MS assay for accurate quantification of mycophenolic acid (MPA) and its glucuronide conjugates in human plasma. Plasma proteins were precipitated with acetonitrile and the chromatographic separation was achieved on a C18 column with a gradient elution. The detection was performed by a triple quadrupole mass spectrometer in the positive electrospray ionization and multiple reaction monitoring mode. Linearity of the assay was demonstrated over the range of 20–10,000 ng/mL for MPA and MPA glucuronide (MPAG), and 2–1000 ng/mL for acyl MPA glucuronide in human plasma. The assay was precise and accurate with coefficient of variation and bias <15%. MPA and MPAG were stable at 25 °C up to 1 day in both heparin- and EDTA-treated blood. In heparin- and EDTA-plasma, MPA and MPAG were stable for at least 1 week at 25 and 4 °C, and 1 month at −20 °C. However, 99% acyl MPA glucuronide degraded in both heparin- and EDTA-blood as well as plasma when stored at room temperature for 1 day. All the analytes remained stable for at least 3 months in acidified EDTA-plasma at −80 °C. The assay was successfully applied on patients post hematopoietic stem cell transplantation.

Original languageEnglish (US)
Pages (from-to)1648-1655
Number of pages8
JournalBiomedical Chromatography
Volume30
Issue number10
DOIs
StatePublished - Oct 1 2016

Keywords

  • acyl mycophenolic acid glucuronide
  • mycophenolic acid
  • mycophenolic acid glucuronide
  • stability
  • UPLC–MS/MS

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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