Determination of a novel B-Raf(V600E) and EGFR dual inhibitor in rat plasma by HPLC-MS/MS and its application in a pharmacokinetic study

J Pharm Biomed Anal. 2016 Sep 10:129:142-147. doi: 10.1016/j.jpba.2016.06.049. Epub 2016 Jun 28.

Abstract

The EGFR and B-Raf(V600E) dual inhibition is a promising strategy in treatment of colorectal cancer patients with B-Raf(V600E) mutation. Previously, compound 3 was designed and synthesized as a novel B-Raf(V600E) 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.

Keywords: EGFR and B-Raf(V600E) dual inhibitor; Pharmacokinetics; Rats.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid / methods
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Female
  • Male
  • Protein Kinase Inhibitors / blood*
  • Protein Kinase Inhibitors / pharmacokinetics*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry / methods*

Substances

  • Protein Kinase Inhibitors
  • Egfr protein, rat
  • ErbB Receptors
  • Proto-Oncogene Proteins B-raf