title: 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.
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.
authors.affiliation: Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China. Electronic address: 397796861@qq.com.
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Zhou
authors.affiliation: School of Bioscience & Bioengineering, South China University of Technology, Guangzhou, 510640, PR China.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Deng
authors.affiliation: Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, #190 Kaiyuan Avenue, Guangzhou 510530, PR China.
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Li
authors.affiliation: University of Macau, Avenue Padre Tomás Pereira Taipa, Macau, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, #190 Kaiyuan Avenue, Guangzhou 510530, PR China. Electronic address: pharma_chemistry@163.com.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D008297:Male; D047428:Protein Kinase Inhibitors / Q000097:blood* / Q000493:pharmacokinetics*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D047428:Protein Kinase Inhibitors; C483803:Egfr protein, rat; D066246:ErbB Receptors; D048493:Proto-Oncogene Proteins B-raf
keywords: EGFR and B-Raf(V600E) dual inhibitor; Pharmacokinetics; Rats