Determination of a novel B-RafV600E and EGFR dual inhibitor in rat plasma by HPLC–MS/MS and its application in a pharmacokinetic study

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Abstract

Graphical abstract

The mean plasma concentration-time profiles of compound 3 after an intravenous dose of 6 mg/kg compound 3 (n = 6) and an oral dose of 15 mg/kg compound 3 for rats (n = 6)

The EGFR and B-RafV600E dual inhibition is a promising strategy in treatment of colorectal cancer patients with B-RafV600E mutation. Previously, compound 3 was designed and synthesized as a novel B-RafV600E and EGFR dual inhibitor with highly potency in both kinase and cell based assay. Herein, a sensitive and rapid HPLC–MS/MS quantitative method was developed and validated for the further pharmacokinetic evaluation of compound 3 in rats.

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