Determination of imatinib mesylate and its main metabolite (CGP74588) in human plasma and murine specimens by ion-pairing reversed-phase high-performance liquid chromatography.
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.
Oostendorp
Roos L
RL
Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
Beijnen
Jos H
JH
Schellens
Jan H M
JH
Tellingen
Olaf van
Ov
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
D001549:Benzamides; C464561:CGP 74588; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate