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

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.

Desnutrição protéica: efeito sobre o espraiamento, fagocitose e atividade fungicida de macrófagos peritoneais / Protein malnutrition: effect on spreading phagocytosis and fungicide activity of peritoneal macrophages

A desnutrição protéico-calórica modifica tanto a resposta imune específica como a inespecífica, predispondo o indivíduo a agentes infecciosos. Neste trabalho avaliamos o efeito da desnutrição protéica sobre o espraiamento, fagocitose e a atividade fungicida de macrófagos peritoneais frente à Candida albicans. Camundongos Swiss, adultos, machos foram divididos em dois grupos: nutrido (controle), alimentado com ração contendo 20 porcento de proteína e grupo desnutrido, que recebeu ração com 4 porcento de proteína. Os macrófagos peritoneais foram ativados por meio da administração intraperitonial de caseinato de sódio 3 porcento. Observamos que macrófagos residentes oriundos de animais desnutridos...

Protein-calorie malnutrition: decrease in the peritonial macrophage's respiratory burst

Protein malnutrition and disease are frequently associated. It modifies both the organism's specific and non-specific immune response to infectious agents. However, the exact mechanisms underlying these findings have not yet been clearly elucidated. In this study, we examined the respiratoy burst capacity in resident and activated peritoneal macrophages obtained from adult male mice who were fed either a control (20 porcent protein) or a low-protein (4 porcent protein) diet. The activated macrophages were obtained after an intra-peritoneal administration of sodium caseinate. Through chemiluminescence assays using either luminol or lucigenin, the kinetics and production...