Determination of serum levels of imatinib mesylate in patients with chronic myeloid leukemia: validation and application of a new analytical method to monitor treatment compliance

• Published in: Revista brasileira de hematologia e hemoterapia Vol. 35; no. 2; pp. 103 - 108
• Main Authors: Rezende, Vinícius Marcondes, Rivellis, Ariane Julio, Gomes, Melissa Medrano, Dörr, Felipe Augusto, Novaes, Mafalda Megumi Yoshinaga, Nardinelli, Luciana, Costa, Ariel Lais de Lima, Chamone, Dalton de Alencar Fisher, Bendit, Israel
• Format: Journal Article
• Language: English
• Published: Brazil Associação Brasileira de Hematologia e Hemoterapia 2013; Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular; Elsevier
• Subjects: Antineoplastic agents; BCR-ABL positive; Chromatography; chronic; HEMATOLOGY; high pressure liquid; Leukemia; Mass spectrometry; MEDICINE, RESEARCH & EXPERIMENTAL; myelogenous; Original; Pyrimidines; Therapeutic drug monitoring; Therapeutic drug monitoring; Antineoplastic agents/administration & dosage; Chromatography, high pressure liquid; Mass spectrometry; Pyrimidines/administration & dosage; Leukemia, myelogenous, chronic, BCR-ABL positive; Pyrimidines; BCR-ABL positive; Leukemia; myelogenous; high pressure liquid; Antineoplastic agents; chronic; Chromatography
• ISSN: 1516-8484; 1806-0870; 1806-0870
• DOI: 10.5581/1516-8484.20130030

The goal of this study was to monitor imatinib mesylate therapeutically in the Tumor Biology Laboratory, Department of Hematology and Hemotherapy, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP). A simple and sensitive method to quantify imatinib and its metabolite (CGP74588) in human serum was developed and fully validated in order to monitor treatment compliance.
The method used to quantify these compounds in serum included protein precipitation extraction followed by instrumental analysis using high performance liquid chromatography coupled with mass spectrometry. The method was validated for several parameters, including selectivity, precision, accuracy, recovery and linearity.
The parameters evaluated during the validation stage exhibited satisfactory results based on the Food and Drug Administration and the Brazilian Health Surveillance Agency (ANVISA) guidelines for validating bioanalytical methods. These parameters also showed a linear correlation greater than 0.99 for the concentration range between 0.500 µg/mL and 10.0 µg/mL and a total analysis time of 13 minutes per sample. This study includes results (imatinib serum concentrations) for 308 samples from patients being treated with imatinib mesylate.
The method developed in this study was successfully validated and is being efficiently used to measure imatinib concentrations in samples from chronic myeloid leukemia patients to check treatment compliance. The imatinib serum levels of patients achieving a major molecular response were significantly higher than those of patients who did not achieve this result. These results are thus consistent with published reports concerning other populations.