Liquid chromatography–tandem mass spectrometric assay for the multikinase inhibitor regorafenib in plasma |
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Authors: | Dino Luethi Selvi Durmus Alfred H Schinkel Jan H M Schellens Jos H Beijnen Rolf W Sparidans |
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Institution: | 1. Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht, The Netherlands;2. The Netherlands Cancer Institute, Division of Molecular Oncology, Amsterdam, The Netherlands;3. The Netherlands Cancer Institute, Department of Clinical Pharmacology, Amsterdam, The Netherlands;4. Slotervaart Hospital, Department of Pharmacy & Pharmacology, Amsterdam, The Netherlands |
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Abstract: | Regorafenib has recently been approved for the treatment of colorectal cancer. A bioanalytical liquid chromatography–tandem mass spectrometric assay for this multikinase inhibitor was developed and validated in plasma. The concentration range of the assay was 25–25,000 ng/mL. Protein precipitation with acetonitrile was used as sample pre‐treatment with sorafenib as internal standard. The extract was diluted with methanol (25%, v/v) and then injected onto the sub‐2 µm particle, bridged ethylsilicia hybrid trifunctional bonded C18 column. Isocratic elution using 0.02% (v/v) formic acid in a methanol–water mixture was used. Compounds were monitored by a triple quadrupole mass spectrometer in the selected reaction monitoring mode after positive electrospray ionization. Double logarithmic calibration was used; within‐day precisions, between‐day precisions, and accuracies were 3.2–9.2, 4.1–12.3 and 94.8–103.0%, respectively. High drug stability was observed under all relevant storage conditions. The assay was used to measure drug concentrations in a pharmacokinetic study in wild‐type FVB mice. Copyright © 2014 John Wiley & Sons, Ltd. |
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Keywords: | regorafenib multikinase inhibitor LC‐MS/MS bioanalytical assay |
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