Development of a liquid chromatography-tandem mass spectrometric method for quantification of mycophenolic acid and its glucuronides in dried blood spot samples

Hiromasa Iboshi, Hiroaki Yamaguchi, Hiroyuki Suzuki, Masafumi Kikuchi, Masaki Tanaka, Shinya Takasaki, Akiko Takahashi, Masamitsu Maekawa, Miki Shimada, Yasushi Matsuda, Yoshinori Okada, Nariyasu Mano

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Personalized immunosuppressive therapy, including accurate drug dosing based on the drug blood level, leads to better clinical outcomes, specifically regarding avoidance of drug-induced adverse effects and maintenance of efficacy. Mycophenolic acid (MPA) is used as an immunosuppressant in transplantation of various solid organs. The aim of this study was to develop a method for quantification of MPA and its metabolites, mycophenolic acid 7-O-glucuronide (MPAG) and mycophenolic acid acyl glucuronide, in dried blood spot (DBS) samples, using liquid chromatography/electrospray ionization/tandem mass spectrometry. Methods: For sample preparation, a microwave-drying approach was used to deactivate enzymes and reduce drying time. Blood volume was calculated in a DBS disk of 3 mm diameter. Concentrations of analytes in plasma from patients receiving mycophenolate mofetil were compared with DBS samples after hematocrit correction. Results: The method yielded good recoveries of all 3 analytes (90.3%-104.2%). Blood volume in the disk was calculated as 3.0 ± 0.2 mL. Linearity over concentration ranges of 0.1-30 mcg/mL MPA, 0.1-200 mcg/mL MPAG, and 0.125-10 mcg/mL mycophenolic acid acyl glucuronide was obtained with r2 ≥0.999. Intraday and interday variations were less than 14.6%, and accuracy was within 611.9%. Passing-Bablok analysis showed no significant differences between plasma concentrations and DBS concentrations after hematocrit correction of MPA and MPAG. Conclusions: We developed and validated a liquid chromatography/electrospray ionization-tandem mass spectrometry method for analysis of MPA in DBS samples. The method is useful for monitoring the MPA blood level.

Original languageEnglish
Pages (from-to)648-653
Number of pages6
JournalTherapeutic drug monitoring
Volume39
Issue number6
DOIs
Publication statusPublished - 2017

Keywords

  • Dried blood spot
  • LC/ESI-MS/MS
  • Mycophenolic acid
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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