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Liquid chromatography–tandem mass spectrometric assay for the multikinase inhibitor regorafenib in plasma
Author(s) -
Luethi Dino,
Durmus Selvi,
Schinkel Alfred H.,
Schellens Jan H. M.,
Beijnen Jos H.,
Sparidans Rolf W.
Publication year - 2014
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3176
Subject(s) - chemistry , chromatography , protein precipitation , triple quadrupole mass spectrometer , formic acid , bioanalysis , regorafenib , selected reaction monitoring , electrospray ionization , mass spectrometry , tandem mass spectrometry , elution , electrospray , liquid chromatography–mass spectrometry , pharmacokinetics , pharmacology , colorectal cancer , cancer , medicine
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 C 18 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.