High-throughput quantification of the anti-leukemia drug STI571 (Gleevec) and its main metabolite (CGP 74588) in human plasma using liquid chromatography-tandem mass spectrometry.

摘要: The signal transduction inhibitor STI571 (formerly known as CGP 57148B) or Gleevec received fast track approval by the US Food and Drug Administration (FDA) for treatment of chronic myeloid leukemia (CML). is a revolutionary promising new oral therapy CML, which functions at molecular level with high specificity. dramatic improvement in efficacy compared to existing treatments prompted an equally profound increase pace development Gleevec. duration from first dose man completion New Application (NDA) filing was approximately 2.6 years. In order support all pharmacokinetics studies sufficient speed meet various target dates, semi-automated procedure using protein precipitation developed validated. A Tomtec Quadra 96 (Model 320) step 96-well plate format were utilized. Sciex API 3000 triple quadrupole mass spectrometer atmospheric pressure chemical ionization interface operated positive ion mode used detection. method proved be rugged allowed simultaneous quantification its main metabolite (CGP 74588) human plasma. Herein, assay development, validation, representative concentration-time profiles obtained clinical are presented.