title: 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.
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.
authors.affiliation: 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
authors.forename: Silvana Aparecida
authors.initials: SA
authors.lastname: Rocco
authors.forename: Jesus Antonio
authors.initials: JA
authors.lastname: Velho
authors.forename: Rodrigo Miguel
authors.initials: RM
authors.lastname: Marin
authors.forename: Luís
authors.initials: L
authors.lastname: de Arruda Rolim Filho
authors.forename: Anibal Eugênio
authors.initials: AE
authors.lastname: Vercesi
authors.forename: Roberto
authors.initials: R
authors.lastname: Rittner
authors.forename: Kleber Gomes
authors.initials: KG
authors.lastname: Franchini
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; C088860:4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline