High-performance liquid chromatographic analysis of the tyrphostin AG1478, a specific inhibitor of the epidermal growth factor receptor tyrosine kinase, in mouse plasma.
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.
Ellis
A G
AG
Pharmacology and Developmental Therapeutics Unit, Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, Melbourne, Victoria, Australia.
Nice
E C
EC
Weinstock
J
J
Levitzki
A
A
Burgess
A W
AW
Webster
L K
LK
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004791:Enzyme Inhibitors / Q000097:blood; D004795:Enzyme Stability; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005615:Freezing; D051379:Mice; D011799:Quinazolines; D012015:Reference Standards; D012680:Sensitivity and Specificity; D020032:Tyrphostins / Q000097:blood* / Q000493:pharmacokinetics
D004791:Enzyme Inhibitors; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D066246:ErbB Receptors