Sensitive and validated LC-MS/MS methods to evaluate mycophenolic acid pharmacokinetics and pharmacodynamics in hematopoietic stem cell transplant patients

Misaki Kawanishi, Ikuko Yano, Kazuaki Yoshimura, Takashi Yamamoto, Sachiyo Hashi, Satohiro Masuda, Tadakazu Kondo, Akifumi Takaori-Kondo, Kazuo Matsubara

研究成果: ジャーナルへの寄稿学術誌査読

24 被引用数 (Scopus)

抄録

Monitoring of pharmacodynamics in addition to pharmacokinetics is one of strategies to individualize mycophenolate mofetil therapy. The purpose of this study was to develop sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for evaluation of the pharmacokinetics and pharmacodynamics of mycophenolic acid (MPA). Concentrations of mycophenolic acid glucuronide (MPAG), mycophenolic acid acyl-glucuronide, as well as unbound MPA and MPAG, were determined, and inosine-5′-monophosphate dehydrogenase activity was calculated by measuring concentrations of produced xanthosine-5′-monophosphate (XMP) and intracellular adenosine-5′-monophosphate after incubation of peripheral blood mononuclear cell (PBMC) lysates. A metal-free MastroTM column and two gradient patterns were used to improve the quantification limit of XMP to 0.1 μm. In the clinical MPA concentration range, the linearity of the calibration curve, inter- and intra-day precision and accuracy satisfied the relevant US Food and Drug Administration guidelines. The MPA concentrations in hematopoietic stem cell transplant (HSCT) patients determined by the enzyme assay and the present LC-MS/MS method showed a good correlation (r2 = 0.95, p < 0.001). In this study, we report sensitive and validated LC-MS/MS methods to evaluate the pharmacokinetics and pharmacodynamics of MPA, which are sufficiently sensitive to assess small quantities of PBMC lysates collected shortly after HSCT.

本文言語英語
ページ(範囲)1309-1316
ページ数8
ジャーナルBiomedical Chromatography
29
9
DOI
出版ステータス出版済み - 9月 1 2015

!!!All Science Journal Classification (ASJC) codes

  • 分析化学
  • 生化学
  • 分子生物学
  • 薬理学
  • 創薬
  • 臨床生化学

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