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 .