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Determination of imatinib mesylate and its main metabolite (CGP74588) in human plasma and murine specimens by ion‐pairing reversed‐phase high‐performance liquid chromatography
Author(s) -
Oostendorp Roos L.,
Beijnen Jos H.,
Schellens Jan H. M.,
Tellingen Olaf van
Publication year - 2007
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.816
Subject(s) - chemistry , chromatography , metabolite , high performance liquid chromatography , calibration curve , ammonium acetate , desmethyl , imatinib mesylate , extraction (chemistry) , solid phase extraction , detection limit , imatinib , biochemistry , immunology , biology , myeloid leukemia
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 × 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 m m 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 µg/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. Copyright © 2007 John Wiley & Sons, Ltd.