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記事

14 引用 (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.

元の言語英語
ページ(範囲)1309-1316
ページ数8
ジャーナルBiomedical Chromatography
29
発行部数9
DOI
出版物ステータス出版済み - 9 1 2015

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Pharmacodynamics
Mycophenolic Acid
Transplants
Pharmacokinetics
Hematopoietic Stem Cells
Stem cells
Blood Cells
Blood
IMP Dehydrogenase
Liquid chromatography
Enzyme Assays
United States Food and Drug Administration
Adenosine Monophosphate
Tandem Mass Spectrometry
Liquid Chromatography
Adenosine
Calibration
Mass spectrometry
Assays
Metals

All Science Journal Classification (ASJC) codes

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

これを引用

Sensitive and validated LC-MS/MS methods to evaluate mycophenolic acid pharmacokinetics and pharmacodynamics in hematopoietic stem cell transplant patients. / Kawanishi, Misaki; Yano, Ikuko; Yoshimura, Kazuaki; Yamamoto, Takashi; Hashi, Sachiyo; Masuda, Satohiro; Kondo, Tadakazu; Takaori-Kondo, Akifumi; Matsubara, Kazuo.

:: Biomedical Chromatography, 巻 29, 番号 9, 01.09.2015, p. 1309-1316.

研究成果: ジャーナルへの寄稿記事

Kawanishi, M, Yano, I, Yoshimura, K, Yamamoto, T, Hashi, S, Masuda, S, Kondo, T, Takaori-Kondo, A & Matsubara, K 2015, 'Sensitive and validated LC-MS/MS methods to evaluate mycophenolic acid pharmacokinetics and pharmacodynamics in hematopoietic stem cell transplant patients', Biomedical Chromatography, 巻. 29, 番号 9, pp. 1309-1316. https://doi.org/10.1002/bmc.3423
Kawanishi, Misaki ; Yano, Ikuko ; Yoshimura, Kazuaki ; Yamamoto, Takashi ; Hashi, Sachiyo ; Masuda, Satohiro ; Kondo, Tadakazu ; Takaori-Kondo, Akifumi ; Matsubara, Kazuo. / Sensitive and validated LC-MS/MS methods to evaluate mycophenolic acid pharmacokinetics and pharmacodynamics in hematopoietic stem cell transplant patients. :: Biomedical Chromatography. 2015 ; 巻 29, 番号 9. pp. 1309-1316.
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AU - Masuda, Satohiro

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