High Performance Liquid Chromatography Analysis of a 4-anilinoquinazoline Derivative (PD153035), a Specific Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in Rat Plasma

J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Mar 25;817(2):297-302. doi: 10.1016/j.jchromb.2004.12.021.

Abstract

The quinazoline derivative, 4-N-(3'-bromo-phenyl)amino-6,7-dimethoxyquinazoline (PD153035), has recently been identified as a potential drug for the treatment of proliferative disease. Here, we report a sensitive high performance liquid chromatography (HPLC)-based quantitative detection method for measurement of PD153035 levels in rat plasma. Sample pretreatment involved a two-step extraction with chloroform. The analytes were separated on a column packed with OmniSpher C18 material and eluted with acetonitrile-0.1 M ammonium acetate, pH 7.2 (70:30, v/v). The column effluent was monitored by UV detection at 330 nm. A linear response was achieved over the concentration range 0.50-100.00 microM using multilevel calibration with an internal standard. The analytical method inter- and intra-run accuracy and precision were better than +/-15%. The lower limit of quantification was 0.50 microM. The method has been applied to study the preclinical pharmacokinetics of this compound in rats.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid / methods*
  • Enzyme Inhibitors / blood*
  • Enzyme Inhibitors / pharmacokinetics
  • ErbB Receptors / antagonists & inhibitors*
  • Male
  • Quinazolines / blood*
  • Quinazolines / pharmacokinetics
  • Rats
  • Rats, Wistar
  • Reference Standards
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Spectrophotometry, Ultraviolet

Substances

  • Enzyme Inhibitors
  • Quinazolines
  • ErbB Receptors
  • 4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline