Liquid chromatography-tandem mass spectrometric assay for the simultaneous determination of the irreversible BTK inhibitor ibrutinib and its dihydrodiol-metabolite in plasma and its application in mouse pharmacokinetic studies
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- 作者：Johannes J.M. Rooda ; j.j.m.rood@uu.nl" class="auth_mail" title="E-mail the corresponding author ; Stephanie van Hoppeb ; Alfred H. Schinkelb ; Jan H.M. Schellensa ; c ; Jos H. Beijnena ; c ; d ; Rolf W. Sparidansa
- 关键词：BCR ; B-cell antigen receptor ; BSA ; bovine serum albumin ; BTK ; Bruton&rsquo ; s tyrosine kinase ; CHMP ; Committee for Medicinal Products for Human Use ; DHI ; dhihydrodiol-ibrutinib ; DMSO ; dimethyl Sulphoxide ; EMA ; European Medicines Agency ; ErbB2 ; receptor tyrosine-protein kinase erbB-2 ; ESI ; electro spray ionization ; FDA ; Food and Drug Administration ; LC&ndash ; MS/MS ; liquid chromatography&ndash ; tandem mass spectrometry ; LLOQ ; lower limit of quantitation ; MRP1 ; multidrug resistance protein 1 ; PP ; pol
- 刊名：Journal of Pharmaceutical and Biomedical Analysis
- 出版年：2016
- 出版时间：25 January 2016
- 年：2016
- 卷：118
- 期：Complete
- 页码：123-131
- 全文大小：1535 K
文摘
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A quick and simple validated method for the quantitative analysis of ibrutinib and its dihydrodiol metabolite was designed.
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Ibrutinib exhibits instability in human plasma, where the acryl moiety is lost.
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In FVB mice, ibrutinib is rapidly eliminated and converted into dihydrodiol-ibrutinib.