title: Liquid chromatographic-mass spectrometric assay for quantitation of imatinib and its main metabolite (CGP 74588) in plasma.
abstract: Imatinib mesylate (Gleevec, Glivec, STI571) is a targeted, small molecule inhibitor of the oncogenes, BCR/ABL and c-KIT, and has striking antitumor activity in patients with chronic myelogenous leukemia or gastrointestinal stromal tumors. We have developed a liquid chromatographic-electrospray ionization mass spectrometric (LC-MS) method for quantifying imatinib and its main metabolite (CGP 74588) in plasma. The assay uses deuterated imatinib as the internal standard; acetonitrile deproteination; a Phenomenex Luna C(18)(2) (5 microm, 50 x 4.6 mm) reversed-phase analytical column; a gradient mobile phase of 0.1% formic acid in methanol and water; and mass spectrometric detection using electrospray positive mode electron ionization. The assay has a lower limit of quantitation (LLOQ) of 30 ng/ml and is linear between 30 and 10000 ng/ml for both imatinib and CGP 74588. We demonstrated the suitability of this assay for imatinib using it to quantify the concentrations of imatinib and CGP 74588 in plasma of a patient given a 200-mg dose of imatinib orally. We believe that this LC-MS assay should be an important tool for future pharmacokinetic studies of imatinib.
authors.affiliation: Program of Molecular Therapeutics and Drug Discovery, University of Pittsburgh Cancer Institute, Biomedical Science Tower, E-1040, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Parise
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hayes
authors.forename: Merrill J
authors.initials: MJ
authors.lastname: Egorin
mesh_terms: D001549:Benzamides; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000097:blood* / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D001549:Benzamides; C464561:CGP 74588; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate