کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1220648 1494617 2016 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
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
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
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
چکیده انگلیسی


• A quick and simple validated method for the quantitative analysis of ibrutinib and its dihydrodiol metabolite was designed.
• Ibrutinib exhibits instability in human plasma, where the acryl moiety is lost.
• In FVB mice, ibrutinib is rapidly eliminated and converted into dihydrodiol-ibrutinib.

A validated simple, fast and sensitive bio-analytical assay for ibrutinib and its dihydrodiol metabolite in human and mouse plasma was set up. Sample preparation was performed by protein precipitation, and addition of the respective deuterated internal standards, followed by LC–MS/MS analysis. Separation was performed on a 3.5 μm particle-size, bridged ethylene hybrid column with gradient elution by 0.1% v/v formic acid and acetonitrile. The full eluate was transferred to an electrospray interface in positive ionization mode, and subsequently analyzed by a triple quadrupole mass spectrometer by selected reaction monitoring. The assay was validated in a 5–5000 ng/ml calibration range. Both ibrutinib and dihydrodiol-ibrutinib were deemed stable under refrigerated or frozen storage conditions. At room temperature, ibrutinib showed a not earlier described instability, and revealed rapid degradation at 37 °C. Finally, the assay was used for a pharmacokinetic study of plasma levels in treated FVB mice.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 118, 25 January 2016, Pages 123–131
نویسندگان
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