High-performance liquid chromatographic analysis of the tyrphostin AG1478, a specific inhibitor of the epidermal growth factor receptor tyrosine kinase, in mouse plasma

A. G. Ellis, E. C. Nice, J. Weinstock, A. Levitzki, A. W. Burgess, L. K. Webster

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Abstract

The tyrphostin 4-(3-chloroanilino)-6,7-dimethoxyquinazoline (AG1478) is undergoing evaluation as a potential new anticancer agent. We have developed a specific and sensitive reversed-phase HPLC assay for AG1478 in mouse plasma. The method involves a rapid and simple extraction process followed by separation on a Symmetry C8 stationary phase with a gradient of acetonitrile in ammonium acetate buffer. A linear response was achieved over the concentration range of 0.2-100 μM using multilevel calibration with internal standard method of calculation. Inter- and intra-assay accuracy and precision were better than ±10%. The limit of quantitation was 0.2 μM. We have used this method to study the preclinical pharmacokinetics of this new agent in mice.

Original languageEnglish
Pages (from-to)193-199
Number of pages7
JournalJournal of Chromatography B: Biomedical Sciences and Applications
Volume754
Issue number1
DOIs
Publication statusPublished - 15 Apr 2001
Externally publishedYes

Keywords

  • AG1478
  • Tyrphostins

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