Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
7615205 | Journal of Chromatography B | 2018 | 13 Pages |
Abstract
A sensitive and selective method of high performance liquid chromatography (HPLC) coupled to tandem mass spectrometry (MS/MS) has been developed for the simultaneous quantification of six anticancer protein kinase inhibitors (PKIs), dabrafenib, trametinib, vemurafenib, cobimetinib, pazopanib, regorafenib, and two active metabolites (regorafenib-M2 and regorafenib-M5) in human plasma. Plasma protein precipitation with methanol enables the sample extraction of 100â¯Î¼L aliquot of plasma. Analytes are detected by electrospray triple-stage quadrupole mass spectrometry and quantified using the calibration curves with stable isotope-labeled internal standards. The method was validated based on FDA recommendations, including assessment of extraction yield (74-104%), matrix effects, analytical recovery (94-104%) with low variability (<15%). The method is sensitive (lower limits of quantification within 1 to 200â¯ng/mL), accurate (intra- and inter-assay bias: â0.3% to +12.7%, and â3.2% to +6.3%, respectively) and precise (intra- and inter-assay CVs within 0.7-7.3% and 2.5-8.0%, respectively) over the clinically relevant concentration range (upper limits of quantification 500 to 100,000â¯ng/mL). This method is applied in our laboratory for both clinical research programs and routine therapeutic drug monitoring service of PKIs.
Related Topics
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Authors
Evelina Cardoso, Thomas Mercier, Anna Dorothea Wagner, Krisztian Homicsko, Olivier Michielin, Kim Ellefsen-Lavoie, Laurène Cagnon, Manuel Diezi, Thierry Buclin, Nicolas Widmer, Chantal Csajka, Laurent Decosterd,