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 meta...
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| Format: | Article |
| Language: | English |
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Elsevier
2013-01-01
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| Series: | Revista Brasileira de Hematologia e Hemoterapia |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-84842013000200011&lng=en&tlng=en |
| _version_ | 1818064095402786816 |
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| author | Vinícius Marcondes Rezende Ariane Julio Rivellis Melissa Medrano Gomes Felipe Augusto Dörr Mafalda Megumi Yoshinaga Novaes Luciana Nardinelli Ariel Lais de Lima Costa Dalton de Alencar Fisher Chamone Israel Bendit |
| author_facet | Vinícius Marcondes Rezende Ariane Julio Rivellis Melissa Medrano Gomes Felipe Augusto Dörr Mafalda Megumi Yoshinaga Novaes Luciana Nardinelli Ariel Lais de Lima Costa Dalton de Alencar Fisher Chamone Israel Bendit |
| author_sort | Vinícius Marcondes Rezende |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T14:30:33Z |
| format | Article |
| id | doaj.art-a1de88ee87a44ead8a839f7700d3940c |
| institution | Directory Open Access Journal |
| issn | 1806-0870 |
| language | English |
| last_indexed | 2024-12-10T14:30:33Z |
| publishDate | 2013-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Revista Brasileira de Hematologia e Hemoterapia |
| spelling | doaj.art-a1de88ee87a44ead8a839f7700d3940c2022-12-22T01:44:56ZengElsevierRevista Brasileira de Hematologia e Hemoterapia1806-08702013-01-0135210310810.5581/1516-8484.20130030S1516-84842013000200011Determination of serum levels of imatinib mesylate in patients with chronic myeloid leukemia: validation and application of a new analytical method to monitor treatment complianceVinícius Marcondes Rezende0Ariane Julio Rivellis1Melissa Medrano Gomes2Felipe Augusto Dörr3Mafalda Megumi Yoshinaga Novaes4Luciana Nardinelli5Ariel Lais de Lima Costa6Dalton de Alencar Fisher Chamone7Israel Bendit8Universidade de São PauloUniversidade de São PauloUniversidade de São PauloUniversidade de São PauloUniversidade de São PauloUniversidade de São PauloUniversidade de São PauloUniversidade de São PauloUniversidade de São PauloOBJECTIVE: 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-84842013000200011&lng=en&tlng=enLeukemiamyelogenouschronicBCR-ABL positiveMass spectrometryChromatographyhigh pressure liquidPyrimidinesAntineoplastic agentsTherapeutic drug monitoring |
| spellingShingle | Vinícius Marcondes Rezende Ariane Julio Rivellis Melissa Medrano Gomes Felipe Augusto Dörr Mafalda Megumi Yoshinaga Novaes Luciana Nardinelli Ariel Lais de Lima Costa Dalton de Alencar Fisher Chamone Israel Bendit 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 Leukemia myelogenous chronic BCR-ABL positive Mass spectrometry Chromatography high pressure liquid Pyrimidines Antineoplastic agents Therapeutic drug monitoring |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Leukemia myelogenous chronic BCR-ABL positive Mass spectrometry Chromatography high pressure liquid Pyrimidines Antineoplastic agents Therapeutic drug monitoring |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-84842013000200011&lng=en&tlng=en |
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