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

4 Citations (Scopus)

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

Fingerprint

Plasma (human)
Metabolites
Mycophenolic Acid
Edetic Acid
Assays
Heparin
Glucuronides
Plasmas
Blood
Electrospray ionization
Mass spectrometers
Stem cells
Blood Proteins
Hematopoietic Stem Cell Transplantation
mycophenolic acid glucuronide
Monitoring
Temperature

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

Cite this

Simultaneous quantification of mycophenolic acid and its glucuronide metabolites in human plasma by an UPLC–MS/MS assay. / Zhang, Daping; Chow, Diana S.L.; Renbarger, Jamie.

In: Biomedical Chromatography, Vol. 30, No. 10, 01.10.2016, p. 1648-1655.

Research output: Contribution to journalArticle

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