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

Revista Brasileira de Hematologia e Hemoterapia

Vinícius Marcondes Rezende¹  Ariane Julio Rivellis¹  Melissa Medrano Gomes¹  Felipe Augusto Dörr¹  Mafalda Megumi Yoshinaga Novaes¹  Luciana Nardinelli¹  Ariel Lais De Lima Costa¹  Dalton De Alencar Fisher Chamone¹  Israel Bendit¹ 

[1] ,Universidade de São Paulo Faculdade de Medicina São Paulo SP ,Brazil

关键词: Leukemia;    myelogenous;    chronic;    BCR-ABL positive;    Mass spectrometry;    Chromatography;    high pressure liquid;    Pyrimidines;    Antineoplastic agents;    Therapeutic drug monitoring;   

DOI  :  10.5581/1516-8484.20130030

来源: SciELO

【 摘 要 】

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

【 授权许可】

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