Article

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

Pharmacology and Developmental Therapeutics Unit, Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, Melbourne, Victoria, Australia.
Journal of chromatography. B, Biomedical sciences and applications 05/2001; 754(1):193-9. pp.193-9
Source: PubMed

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 microM 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 microM. We have used this method to study the preclinical pharmacokinetics of this new agent in mice.

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Keywords

ammonium acetate buffer
 
concentration range
 
internal standard method
 
mouse plasma
 
multilevel calibration
 
new agent
 
potential new anticancer agent
 
preclinical pharmacokinetics
 
sensitive reversed-phase HPLC assay
 
simple extraction process
 
Symmetry C8 stationary phase
 
tyrphostin 4-(3-chloroanilino)-6,7-dimethoxyquinazoline