title: Development and validation of a sensitive assay for the quantification of imatinib using LC/LC-MS/MS in human whole blood and cell culture.
abstract: We developed and validated a semi-automated LC/LC-MS/MS assay for the quantification of imatinib in human whole blood and leukemia cells. After protein precipitation, samples were injected into the HPLC system and trapped onto the enrichment column (flow 5 mL/min); extracts were back-flushed onto the analytical column. Ion transitions [M + H](+) of imatinib (m/z = 494.3 --> 394.3) and its internal standard trazodone (372.5 --> 176.3) were monitored. The range of reliable response was 0.03-75 ng/mL. The inter-day precisions were: 8.4% (0.03 ng/mL), 7.2% (0.1 ng/mL), 6.5% (1 ng/mL), 8.2% (10 ng/mL) and 4.3% (75 ng/mL) with no interference from ion suppression. Autosampler stability was 24 hs and samples were stable over three freeze-thaw cycles. This semi-automated method is simple with only one manual step, uses a commercially available internal standard, and has proven to be robust in larger studies.
authors.affiliation: Clinical Research and Development, Department of Anesthesiology, University of Colorado Denver, Aurora, CO 80045-7503, USA. Jelena.Klawitter@ucdenver.edu
authors.forename: Jelena
authors.initials: J
authors.lastname: Klawitter
authors.forename: Yan Ling
authors.initials: YL
authors.lastname: Zhang
authors.forename: Jost
authors.initials: J
authors.lastname: Klawitter
authors.forename: Nora
authors.initials: N
authors.lastname: Anderson
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Serkova
authors.forename: Uwe
authors.initials: U
authors.lastname: Christians
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood*; D001549:Benzamides; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D000068877:Imatinib Mesylate; D057230:Limit of Detection; D010879:Piperazines / Q000097:blood*; D011743:Pyrimidines / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate