title: Imatinib assay by high-performance liquid chromatography in tandem mass spectrometry with solid-phase extraction in human plasma.
abstract: We have developed a method of liquid chromatography in tandem with mass spectrometry to monitor therapeutic levels of imatinib in plasma, a selective inhibitor of protein tyrosine kinase. After solid-phase extraction of plasma samples, imatinib and its internal standard, imatinib-D8, were eluted with Zorbax SB-C18 at 60 °C, under isocratic conditions through a mobile phase consisting of 4 mm ammonium formate, pH: 3.2 (solution A) and acetonitrile solution B. The flow rate was 0.8 mL/min with 55% solution A + 45% solution B. Imatinib was detected and quantified by mass spectrometry with electrospray ionization operating in selected-reaction monitoring mode. The calibration curve was linear in the range 10-5000 ng/mL, the lower limit of quantitation being 10 ng/mL. The method was validated according to the recommendations of the Food and Drug Administration, including tests of matrix effect (bias < 10%) and recovery efficiency (>80 and <120%). The method is precise (coefficient of variance intra-day <2% and inter-day <7%), accurate (95-108%), sensitive and specific. It is a simple method with very fast recording time (1.2 min) that is applicable to clinical practice. This will permit improvement of the pharmacological treatment of patients.
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Jose María
authors.initials: JM
authors.lastname: Moreno
authors.forename: Aneta
authors.initials: A
authors.lastname: Wojnicz
authors.forename: Juan Luis
authors.initials: JL
authors.lastname: Steegman
authors.forename: Maria F
authors.initials: MF
authors.lastname: Cano-Abad
authors.forename: Ana
authors.initials: A
authors.lastname: Ruiz-Nuño
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood*; D001549:Benzamides / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D057230:Limit of Detection; D010879:Piperazines / Q000097:blood*; D047428:Protein Kinase Inhibitors / Q000097:blood*; D011743:Pyrimidines / Q000097:blood*; D052616:Solid Phase Extraction / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate