title: Determination of imatinib mesylate and its main metabolite (CGP74588) in human plasma and murine specimens by ion-pairing reversed-phase high-performance liquid chromatography.
abstract: A sensitive reversed-phase high-performance liquid chromatographic (HPLC) method has been developed and validated for the determination of imatinib, a tyrosine kinase inhibitor, and its main metabolite N-desmethyl-imatinib (CGP74588) in human plasma and relevant murine biological matrices. A simple HPLC assay for the individual quantification of imatinib and CGP74588 in murine specimens has not been reported to date. Sample pre-treatment involved liquid-liquid extraction with tert-butyl-methyl ether. Imatinib, CGP74588 (metabolite) and the internal standard 4-hydroxybenzophenone were separated using a narrow bore (2.1 x 150 mm) stainless steel Symmetry C(18) column and detected by UV at 265 nm. The mobile phase consisted of 28% (v/v) acetonitrile in 50 mM ammonium acetate buffer pH 6.8 containing 0.005 M 1-octane sulfonic acid and was delivered at 0.2 mL/min. The calibration curve was prepared in blank human plasma and was linear over the dynamic range 10 ng/mL to 10 microg/mL). The accuracy was close to 100% and the within-day and between-day precisions were within the generally accepted 15% range. The validation results showed that the assay was selective and reproducible. This method was applied to study the pharmacokinetics of imatinib and its main metabolite in human and mice.
authors: Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
authors: Roos L
authors: RL
authors: Oostendorp
authors: Jos H
authors: JH
authors: Beijnen
authors: Jan H M
authors: JH
authors: Schellens
authors: Olaf van
authors: Ov
authors: Tellingen
mesh_terms: D000818:Animals; D001549:Benzamides; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D051379:Mice; D010879:Piperazines / Q000097:blood*; D011743:Pyrimidines / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods
chemical_list: D001549:Benzamides; C464561:CGP 74588; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate