Imunossensor impedimétrico para determinação de rituximabe aplicado ao controle qualidade e monitoramento clínico
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFG |
dARK ID: | ark:/38995/0013000005z06 |
Texto Completo: | http://repositorio.bc.ufg.br/tede/handle/tede/12938 |
Resumo: | Introduction: Cancer is an umbrella term for a large group of diseases that can affect any part of the body. Rituximab (RTX) is a chimeric monoclonal antibody (mAb) formed by the mouse/human combination, which specifically binds to the CD20 cell marker that is expressed in normal and malignant B lymphocytes, exerting significant antitumor activity. In this context, RTX emerged as a therapeutic alternative in the treatment of various pathologies, including autoimmune diseases, inflammatory diseases and various types of cancer in which sensitive and low-cost methods are required for therapeutic drug monitoring (TDM) and quality control (QC) of this drug. Objectives: To develop a selective electrochemical immunosensor for the detection and quantification of RTX in urine and blood. Methodology: The ploliconal antibody (pAb) was purified from chicken egg, used as a biorecognition element to create an immunosensor for the detection and quantification of RTX. The immunosensor was constructed from the immobilization of the RTX IgY antibody on the glassy carbon electrode surfaces. The characterization of the immunosensor was obtained through monitoring at each stage via cyclic voltammetry and electrochemical impedance spectroscopy, where selectivity is obtained by specifically binding pAb and RTX and casein is used to block possible nonspecific interactions of other proteins. After the development of the immunosensor, the validation of the method was carried out, evaluating the selectivity, accuracy, precision, linearity and limits of detection (LOD) and quantification (LOQ). Finally, the RTX was determined in urine and blood samples. Results and discussion: Linearity was demonstrated between charge transfer resistance and RTX from 2 to 14 μg mL−1 (r2 of 0.99), with LOD and LOQ of 130 and 400 ng mL−1 respectively. The method showed adequate precision with a RPD of 0.96% for researcher 1 and 1.27% for researcher 2, and accuracy with a RPD of 1.30%, with a confidence interval between 99.0% and 101.0 %. Selectivity was achieved by demonstrating the binding specificity between the antibody and RTX, where casein blocks non-specific binding when the immunosensor is applied to blood and urine samples. Conclusion: The developed immunosensor presented precision and accuracy for the detection of RTX with results in approximately 20 minutes. In this way, low-cost, marker-sensitive electrochemical immunosensors can help in TDM, QC and extended stability monitoring of different drugs, in a simple way and with versatile assays. |
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Gil, Eric de Souzahttp://lattes.cnpq.br/3218622824233303Neves, Bruno Júniorhttp://lattes.cnpq.br/7256565904920282Gil, Eric de SouzaSgobbi, Lívia FlórioFeres, Valeria Christina De RezendeOliveira Neto, Jerônimo Raimundo deFerreira Júnior, Álvarohttp://lattes.cnpq.br/0626957028228867Rodrigues, Edson Silvio Batista2023-07-06T11:01:59Z2023-07-06T11:01:59Z2023-02-10RODRIGUES, E. S. B. Imunossensor impedimétrico para determinação de rituximabe aplicado ao controle qualidade e monitoramento clínico. 2023. 58 f. Tese (Doutorado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2023.http://repositorio.bc.ufg.br/tede/handle/tede/12938ark:/38995/0013000005z06Introduction: Cancer is an umbrella term for a large group of diseases that can affect any part of the body. Rituximab (RTX) is a chimeric monoclonal antibody (mAb) formed by the mouse/human combination, which specifically binds to the CD20 cell marker that is expressed in normal and malignant B lymphocytes, exerting significant antitumor activity. In this context, RTX emerged as a therapeutic alternative in the treatment of various pathologies, including autoimmune diseases, inflammatory diseases and various types of cancer in which sensitive and low-cost methods are required for therapeutic drug monitoring (TDM) and quality control (QC) of this drug. Objectives: To develop a selective electrochemical immunosensor for the detection and quantification of RTX in urine and blood. Methodology: The ploliconal antibody (pAb) was purified from chicken egg, used as a biorecognition element to create an immunosensor for the detection and quantification of RTX. The immunosensor was constructed from the immobilization of the RTX IgY antibody on the glassy carbon electrode surfaces. The characterization of the immunosensor was obtained through monitoring at each stage via cyclic voltammetry and electrochemical impedance spectroscopy, where selectivity is obtained by specifically binding pAb and RTX and casein is used to block possible nonspecific interactions of other proteins. After the development of the immunosensor, the validation of the method was carried out, evaluating the selectivity, accuracy, precision, linearity and limits of detection (LOD) and quantification (LOQ). Finally, the RTX was determined in urine and blood samples. Results and discussion: Linearity was demonstrated between charge transfer resistance and RTX from 2 to 14 μg mL−1 (r2 of 0.99), with LOD and LOQ of 130 and 400 ng mL−1 respectively. The method showed adequate precision with a RPD of 0.96% for researcher 1 and 1.27% for researcher 2, and accuracy with a RPD of 1.30%, with a confidence interval between 99.0% and 101.0 %. Selectivity was achieved by demonstrating the binding specificity between the antibody and RTX, where casein blocks non-specific binding when the immunosensor is applied to blood and urine samples. Conclusion: The developed immunosensor presented precision and accuracy for the detection of RTX with results in approximately 20 minutes. In this way, low-cost, marker-sensitive electrochemical immunosensors can help in TDM, QC and extended stability monitoring of different drugs, in a simple way and with versatile assays.Introdução: Câncer é um termo genérico para um grande grupo de doenças que pode afetar qualquer parte do corpo. O Rituximabe (RTX) é um anticorpo monoclonal (mAb) químerico formado pela combinação camundongo/humano, que se liga especificamente ao marcador da célula CD20 que é expresso em linfócitos B normais e malignos, exercendo atividade antitumoral significativa. Nesse contexo o RTX surgiu como alternativa terapêutica no tratamento de várias patologias, incluindo doenças autoimunes, doenças inflamatórias e diversos tipos de câncer no qual é necessário métodos sensíveis e de baixo custo para o monitoramento terapêutico de fármacos (TDM) e controle de qualidade (CQ) desse medicamento. Objetivo: Desenvolver um imunossensor eletroquímico seletivo para a detecção e quantificação de RTX na urina e sangue. Metodologia: O anticorpo ploliconal (pAb) foi purificado a partir de ovo de galinha, usado como elemento de bioreconhecimento para criar um imunossensor para a detecção e quantificação de RTX. O imunossensor foi construído apartir da imobilização do anticorpo IgY de RTX nas superfícies do eletrodo de carbono vítreo. A caracterização do imunossensor foi obtida atravez do monitoramento em cada etapa via voltametria cíclica e espectroscopia de impedância eletroquímica, onde a seletividade é obtida pela ligação especifica em o pAb e o RTX e a caseína é utilizada para bloquear possíveis interações inespecífica de outras protéinas. Após o desenvolvimento do imunossensor foi realizado a validação do método, avaliando a seletividade, exatidão, precisão, linearidade e os limites de detecção (LOD) e quantificação (LOQ). Por fim foi determinado o RTX em amostras de urina e sangue. Resultados e discussões: Foi demonstrado a linearidade entre a resistência de transferência de carga e RTX de 2 a 14 μg mL −1 (r2 de 0,99), com LOD e LOQ de 130 e 400 ng mL −1 respectivamente. O método apresentou precisão adequada com DPR de 0,96% para o pesquisador 1 e 1,27% para o pesquisador 2, e exatidão com DPR de 1,30%, com um intervalo de confiaça entre 99,0% a 101,0%. A seletividade foi alcançada demonstrando a especificidade da ligação entre o anticorpo e o RTX, onde a caseína bloqueia ligações inespecíficas quando o imunosensor é aplicado em amostras de sangue e urina. Conclusões: O imunossensor desenvolvido apresentou precisão e exatidão para a detecção de RTX com resultados em aproximadamente 20 minutos. Dessa forma imunossensores eletroquímicos de baixo custo, com marcadores e sensíveis podem auxiliar no TDM, CQ e monitoramento de estabilidade estendida de diferentes medicamentos, de maneira simples e com ensaios versáteis.Submitted by Dayane Basílio (dayanebasilio@ufg.br) on 2023-07-05T13:50:16Z No. of bitstreams: 2 Tese - Edson Silvio Batista Rodrigues - 2023.pdf: 4287216 bytes, checksum: 4c570f0fa1fc21d080d459232661d954 (MD5) license_rdf: 805 bytes, checksum: 4460e5956bc1d1639be9ae6146a50347 (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2023-07-06T11:01:59Z (GMT) No. of bitstreams: 2 Tese - Edson Silvio Batista Rodrigues - 2023.pdf: 4287216 bytes, checksum: 4c570f0fa1fc21d080d459232661d954 (MD5) license_rdf: 805 bytes, checksum: 4460e5956bc1d1639be9ae6146a50347 (MD5)Made available in DSpace on 2023-07-06T11:01:59Z (GMT). No. of bitstreams: 2 Tese - Edson Silvio Batista Rodrigues - 2023.pdf: 4287216 bytes, checksum: 4c570f0fa1fc21d080d459232661d954 (MD5) license_rdf: 805 bytes, checksum: 4460e5956bc1d1639be9ae6146a50347 (MD5) Previous issue date: 2023-02-10porUniversidade Federal de GoiásPrograma de Pós-graduação em Ciências Farmacêuticas (FF)UFGBrasilFaculdade de Farmácia - FF (RMG)Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessImunoensaioProteína CD20Espectroscopia de impedância eletroquímicaMonitoramento terapêutico de fármacosTestes on-siteImmunoassayCD20 proteinElectrochemical impedance spectroscopyTherapeutic drug monitoringOn-site testingCIENCIAS DA SAUDE::FARMACIA::FARMACOTECNIAImunossensor impedimétrico para determinação de rituximabe aplicado ao controle qualidade e monitoramento clínicoImpedimetric immunosensor for rituximab innocence applied to quality control and clinical monitoringinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis2750050050022516reponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805http://repositorio.bc.ufg.br/tede/bitstreams/a4882cc5-2405-4575-8d80-38fd22993c95/download4460e5956bc1d1639be9ae6146a50347MD52ORIGINALTese - Edson Silvio Batista Rodrigues - 2023.pdfTese - Edson Silvio Batista Rodrigues - 2023.pdfapplication/pdf4287216http://repositorio.bc.ufg.br/tede/bitstreams/d314cd79-0734-49aa-b6cc-65c589e848af/download4c570f0fa1fc21d080d459232661d954MD53LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.bc.ufg.br/tede/bitstreams/841d0a94-fff2-4909-92f0-756bfbc79970/download8a4605be74aa9ea9d79846c1fba20a33MD51tede/129382023-07-06 08:01:59.825http://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internationalopen.accessoai:repositorio.bc.ufg.br:tede/12938http://repositorio.bc.ufg.br/tedeRepositório InstitucionalPUBhttp://repositorio.bc.ufg.br/oai/requesttasesdissertacoes.bc@ufg.bropendoar:2023-07-06T11:01:59Repositório Institucional da UFG - Universidade Federal de Goiás (UFG)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 |
dc.title.pt_BR.fl_str_mv |
Imunossensor impedimétrico para determinação de rituximabe aplicado ao controle qualidade e monitoramento clínico |
dc.title.alternative.eng.fl_str_mv |
Impedimetric immunosensor for rituximab innocence applied to quality control and clinical monitoring |
title |
Imunossensor impedimétrico para determinação de rituximabe aplicado ao controle qualidade e monitoramento clínico |
spellingShingle |
Imunossensor impedimétrico para determinação de rituximabe aplicado ao controle qualidade e monitoramento clínico Rodrigues, Edson Silvio Batista Imunoensaio Proteína CD20 Espectroscopia de impedância eletroquímica Monitoramento terapêutico de fármacos Testes on-site Immunoassay CD20 protein Electrochemical impedance spectroscopy Therapeutic drug monitoring On-site testing CIENCIAS DA SAUDE::FARMACIA::FARMACOTECNIA |
title_short |
Imunossensor impedimétrico para determinação de rituximabe aplicado ao controle qualidade e monitoramento clínico |
title_full |
Imunossensor impedimétrico para determinação de rituximabe aplicado ao controle qualidade e monitoramento clínico |
title_fullStr |
Imunossensor impedimétrico para determinação de rituximabe aplicado ao controle qualidade e monitoramento clínico |
title_full_unstemmed |
Imunossensor impedimétrico para determinação de rituximabe aplicado ao controle qualidade e monitoramento clínico |
title_sort |
Imunossensor impedimétrico para determinação de rituximabe aplicado ao controle qualidade e monitoramento clínico |
author |
Rodrigues, Edson Silvio Batista |
author_facet |
Rodrigues, Edson Silvio Batista |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Gil, Eric de Souza |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/3218622824233303 |
dc.contributor.advisor-co1.fl_str_mv |
Neves, Bruno Júnior |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/7256565904920282 |
dc.contributor.referee1.fl_str_mv |
Gil, Eric de Souza |
dc.contributor.referee2.fl_str_mv |
Sgobbi, Lívia Flório |
dc.contributor.referee3.fl_str_mv |
Feres, Valeria Christina De Rezende |
dc.contributor.referee4.fl_str_mv |
Oliveira Neto, Jerônimo Raimundo de |
dc.contributor.referee5.fl_str_mv |
Ferreira Júnior, Álvaro |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/0626957028228867 |
dc.contributor.author.fl_str_mv |
Rodrigues, Edson Silvio Batista |
contributor_str_mv |
Gil, Eric de Souza Neves, Bruno Júnior Gil, Eric de Souza Sgobbi, Lívia Flório Feres, Valeria Christina De Rezende Oliveira Neto, Jerônimo Raimundo de Ferreira Júnior, Álvaro |
dc.subject.por.fl_str_mv |
Imunoensaio Proteína CD20 Espectroscopia de impedância eletroquímica Monitoramento terapêutico de fármacos Testes on-site |
topic |
Imunoensaio Proteína CD20 Espectroscopia de impedância eletroquímica Monitoramento terapêutico de fármacos Testes on-site Immunoassay CD20 protein Electrochemical impedance spectroscopy Therapeutic drug monitoring On-site testing CIENCIAS DA SAUDE::FARMACIA::FARMACOTECNIA |
dc.subject.eng.fl_str_mv |
Immunoassay CD20 protein Electrochemical impedance spectroscopy Therapeutic drug monitoring On-site testing |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::FARMACIA::FARMACOTECNIA |
description |
Introduction: Cancer is an umbrella term for a large group of diseases that can affect any part of the body. Rituximab (RTX) is a chimeric monoclonal antibody (mAb) formed by the mouse/human combination, which specifically binds to the CD20 cell marker that is expressed in normal and malignant B lymphocytes, exerting significant antitumor activity. In this context, RTX emerged as a therapeutic alternative in the treatment of various pathologies, including autoimmune diseases, inflammatory diseases and various types of cancer in which sensitive and low-cost methods are required for therapeutic drug monitoring (TDM) and quality control (QC) of this drug. Objectives: To develop a selective electrochemical immunosensor for the detection and quantification of RTX in urine and blood. Methodology: The ploliconal antibody (pAb) was purified from chicken egg, used as a biorecognition element to create an immunosensor for the detection and quantification of RTX. The immunosensor was constructed from the immobilization of the RTX IgY antibody on the glassy carbon electrode surfaces. The characterization of the immunosensor was obtained through monitoring at each stage via cyclic voltammetry and electrochemical impedance spectroscopy, where selectivity is obtained by specifically binding pAb and RTX and casein is used to block possible nonspecific interactions of other proteins. After the development of the immunosensor, the validation of the method was carried out, evaluating the selectivity, accuracy, precision, linearity and limits of detection (LOD) and quantification (LOQ). Finally, the RTX was determined in urine and blood samples. Results and discussion: Linearity was demonstrated between charge transfer resistance and RTX from 2 to 14 μg mL−1 (r2 of 0.99), with LOD and LOQ of 130 and 400 ng mL−1 respectively. The method showed adequate precision with a RPD of 0.96% for researcher 1 and 1.27% for researcher 2, and accuracy with a RPD of 1.30%, with a confidence interval between 99.0% and 101.0 %. Selectivity was achieved by demonstrating the binding specificity between the antibody and RTX, where casein blocks non-specific binding when the immunosensor is applied to blood and urine samples. Conclusion: The developed immunosensor presented precision and accuracy for the detection of RTX with results in approximately 20 minutes. In this way, low-cost, marker-sensitive electrochemical immunosensors can help in TDM, QC and extended stability monitoring of different drugs, in a simple way and with versatile assays. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-07-06T11:01:59Z |
dc.date.available.fl_str_mv |
2023-07-06T11:01:59Z |
dc.date.issued.fl_str_mv |
2023-02-10 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
RODRIGUES, E. S. B. Imunossensor impedimétrico para determinação de rituximabe aplicado ao controle qualidade e monitoramento clínico. 2023. 58 f. Tese (Doutorado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2023. |
dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/12938 |
dc.identifier.dark.fl_str_mv |
ark:/38995/0013000005z06 |
identifier_str_mv |
RODRIGUES, E. S. B. Imunossensor impedimétrico para determinação de rituximabe aplicado ao controle qualidade e monitoramento clínico. 2023. 58 f. Tese (Doutorado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2023. ark:/38995/0013000005z06 |
url |
http://repositorio.bc.ufg.br/tede/handle/tede/12938 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
27 |
dc.relation.confidence.fl_str_mv |
500 500 500 |
dc.relation.department.fl_str_mv |
22 |
dc.relation.cnpq.fl_str_mv |
516 |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.publisher.program.fl_str_mv |
Programa de Pós-graduação em Ciências Farmacêuticas (FF) |
dc.publisher.initials.fl_str_mv |
UFG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Faculdade de Farmácia - FF (RMG) |
publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFG instname:Universidade Federal de Goiás (UFG) instacron:UFG |
instname_str |
Universidade Federal de Goiás (UFG) |
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UFG |
institution |
UFG |
reponame_str |
Repositório Institucional da UFG |
collection |
Repositório Institucional da UFG |
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MD5 MD5 MD5 |
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Repositório Institucional da UFG - Universidade Federal de Goiás (UFG) |
repository.mail.fl_str_mv |
tasesdissertacoes.bc@ufg.br |
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1815172572874014720 |