Liquid Chromatography-Mass Spectrometry/Mass Spectrometry Analysis and Pharmacokinetic Assessment of Ponatinib in Sprague-Dawley Rats.

ABSTRACT:

Introduction

By means of liquid-liquid extraction with ethyl acetate, a rapid, sensitive, and specific LC-MS/MS method was developed and validated for assaying ponatinib and the internal standard, warfarin.

Methods

The method was verified and successfully applied to evaluate the pharmacokinetics of ponatinib in Sprague-Dawley rats.

Results

Ponatinib showed dose-dependent exposure in the circulation system, and the absolute bioavailabilities of ponatinib were 43.95 ± 2.40%, 47.69 ± 5.08% and 55.02 ± 2.50% after intragastric administration of 7.5, 15.0 and 30.0 mg/kg ponatinib in rats, respectively. After consecutive administration at 3.75 mg/kg for 7 days, there was distinct accumulation of ponatinib (AUC_0-∞ = 5479.41 ± 757.07 μg h/L) relative to that of a s

SUBMITTER: Wang P 

PROVIDER: S-EPMC5315062 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature