title: Simultaneous quantification of mycophenolic acid and its glucuronide metabolites in human plasma by an UPLC-MS/MS assay.
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. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, 77030, USA.
authors.forename: Daping
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, 77030, USA.
authors.forename: Diana S-L
authors.initials: DS
authors.lastname: Chow
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Renbarger
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D020719:Glucuronides / Q000097:blood*; D006801:Humans; D009173:Mycophenolic Acid / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D020719:Glucuronides; D009173:Mycophenolic Acid
keywords: UPLC-MS/MS; acyl mycophenolic acid glucuronide; mycophenolic acid; mycophenolic acid glucuronide; stability