Liquid chromatography–tandem mass spectrometric assay for the multikinase inhibitor regorafenib in plasma

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.