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.
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.
Rocco
Silvana Aparecida
SA
Department of Internal Medicine, School of Medicine, Universidade Estadual de Campinas (UNICAMP), Zeferino Vaz Street, Barao Geraldo, 13083-970 Campinas, Sao Paulo, Brazil. srocco@fcm.unicamp.br
Velho
Jesus Antonio
JA
Marin
Rodrigo Miguel
RM
de Arruda Rolim Filho
Luís
L
Vercesi
Anibal Eugênio
AE
Rittner
Roberto
R
Franchini
Kleber Gomes
KG
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004791:Enzyme Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D008297:Male; D011799:Quinazolines / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
D004791:Enzyme Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; C088860:4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline