کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1211841 1494024 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A novel approach for the simultaneous quantification of 18 small molecule kinase inhibitors in human plasma: A platform for optimised KI dosing
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
A novel approach for the simultaneous quantification of 18 small molecule kinase inhibitors in human plasma: A platform for optimised KI dosing
چکیده انگلیسی
Small molecule kinase inhibitors (KIs) are a rapidly expanding class of narrow therapeutic index antineoplastic drugs that exhibit substantial inter-individual variability in exposure. This manuscript describes a novel approach for the quantification of 18 KIs in plasma, providing a platform that is unparalleled in terms of scope for the assessment of KI therapeutic drug monitoring (TDM) and facilitating pharmacokinetic studies with KIs. Following the addition of a panel of four deuterated internal standards, plasma samples were prepared by solvent precipitation with acidified methanol. Analytes were separated on a Waters ACQUITY⿢ T3 HSS C18 analytical column (150 ÿ 2.1 mm, 1.8 μm particle size) by linear gradient elution, with subsequent detection by time-of-flight mass spectrometry. Time-of-flight data were collected in wide pass mode, with selected ion (pseudo-MRM) spectra extracted at the precursor m/z of analytes in ESI+ mode. The analytical performance of this approach in terms of specificity, linearity, accuracy, precision range, quantification limit and detection limit meet all criteria for an analytical platform for the quantification of drugs. This approach was developed, validated and reported in accordance with the 2015 version of the FDA guidance for industry on ⿿analytical procedures are methods validation for drugs and biologics⿿ facilitating direct application as a clinical trials platform.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography B - Volumes 1033–1034, 15 October 2016, Pages 17-26
نویسندگان
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