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タイトル: | Sensitive and validated LC-MS/MS methods to evaluate mycophenolic acid pharmacokinetics and pharmacodynamics in hematopoietic stem cell transplant patients. |
著者: | Kawanishi, Misaki Yano, Ikuko Yoshimura, Kazuaki Yamamoto, Takashi Hashi, Sachiyo Masuda, Satohiro Kondo, Tadakazu https://orcid.org/0000-0002-8959-6271 (unconfirmed) Takaori-Kondo, Akifumi Matsubara, Kazuo |
著者名の別形: | 矢野, 育子 |
キーワード: | mycophenolic acid IMPDH LC-MS/MS therapeutic drug monitoring |
発行日: | Sep-2015 |
出版者: | wiley |
誌名: | Biomedical chromatography |
巻: | 29 |
号: | 9 |
開始ページ: | 1309 |
終了ページ: | 1316 |
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 Mastro(TM) 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 (r(2) = 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. |
記述: | Article first published online: 26 JAN 2015 |
著作権等: | This is the peer reviewed version of the following article: Kawanishi, M., Yano, I., Yoshimura, K., Yamamoto, T., Hashi, S., Masuda, S., Kondo, T., Takaori-Kondo, A., and Matsubara, K. (2015) Sensitive and validated LC-MS/MS methods to evaluate mycophenolic acid pharmacokinetics and pharmacodynamics in hematopoietic stem cell transplant patients. Biomed. Chromatogr., 29: 1309–1316, which has been published in final form at http://dx.doi.org/10.1002/bmc.3423. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. The full-text file will be made open to the public on 26 JAN 2016 in accordance with publisher's 'Terms and Conditions for Self-Archiving'. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/202094 |
DOI(出版社版): | 10.1002/bmc.3423 |
PubMed ID: | 25624121 |
出現コレクション: | 学術雑誌掲載論文等 |
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