Desenvolvimento de método analítico por cromatografia líquida para determinação de impurezas no iodixanol
Ano de defesa: | 2013 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de São Carlos
|
Programa de Pós-Graduação: |
Programa de Pós-Graduação de Mestrado Profissional em Química - PPGQ
|
Departamento: |
Não Informado pela instituição
|
País: |
BR
|
Palavras-chave em Português: | |
Área do conhecimento CNPq: | |
Link de acesso: | https://repositorio.ufscar.br/handle/ufscar/6653 |
Resumo: | This work describes for the first time an isocratic method in a single analytical run to quantify deacetyl iodixanol (iodixanol related compound C), iopentol (iodixanol related compound D) and cyclized iodixanol (iodixanol related compound E), as impurities in iodixanol. Iodixanol is a drug substance, dimeric, nonionic, water-soluble, used as a radiographic contrast medium, which is administered by intravascular injection. The impurities A and B were not evaluated in this work, since they are not commercially available as standards. The method was also validated for the quantitative assay, since there is no chromatographic method described in the current USP compendium for the assay. The impurities can be formed during the synthesis process of iodixanol, and it is important to quantify them due to their related toxicity. In this work, the reverse and hydrophilic interaction (HILIC) modes of elution were evaluated. The hydrophilic elution mode was selected due to good efficiency and selectivity. In both modes of elution, columns having the technology fused-core were used, since they demonstrate high efficiency due to their better mass transfer in comparison to conventional HPLC columns. The chromatographic separation was carried out on a kinetex® HILIC column (150 x 4.6 mm; 2.6 μm) at 20 °C using acetonitrile-formic acid (pH 3.2; 1.0 mmol L-1) (92:08, v/v) at a flow rate of 0.8 mL/min. The compounds were monitored at 243 nm and the total time of analysis was 45 min. The method was validated in accordance with the current ICH guidelines for determination of impurities which include selectivity, linearity, accuracy, precision, limits of quantification and detection and robustness. The limits of quantification (LOQ) were 0.479; 0.0606 and 0.133 μg/mL for the impurities C, D and E, respectively. Furthermore, the validated methods were tested in iodixanol samples. The test results of the analyses of impurities and assay in those samples are presented and discussed accordingly. |
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Rondon, Bruno DoratiotoCass, Quezia Bezerrahttp://genos.cnpq.br:12010/dwlattes/owa/prc_imp_cv_int?f_cod=K4781559E62016-06-02T20:37:48Z2013-12-042016-06-02T20:37:48Z2013-10-17RONDON, Bruno Doratioto. Analytical method development by high performace liquid chromatography for determination of impurities in iodixanol. 2013. 97 f. Dissertação (Mestrado em Ciências Exatas e da Terra) - Universidade Federal de São Carlos, São Carlos, 2013.https://repositorio.ufscar.br/handle/ufscar/6653This work describes for the first time an isocratic method in a single analytical run to quantify deacetyl iodixanol (iodixanol related compound C), iopentol (iodixanol related compound D) and cyclized iodixanol (iodixanol related compound E), as impurities in iodixanol. Iodixanol is a drug substance, dimeric, nonionic, water-soluble, used as a radiographic contrast medium, which is administered by intravascular injection. The impurities A and B were not evaluated in this work, since they are not commercially available as standards. The method was also validated for the quantitative assay, since there is no chromatographic method described in the current USP compendium for the assay. The impurities can be formed during the synthesis process of iodixanol, and it is important to quantify them due to their related toxicity. In this work, the reverse and hydrophilic interaction (HILIC) modes of elution were evaluated. The hydrophilic elution mode was selected due to good efficiency and selectivity. In both modes of elution, columns having the technology fused-core were used, since they demonstrate high efficiency due to their better mass transfer in comparison to conventional HPLC columns. The chromatographic separation was carried out on a kinetex® HILIC column (150 x 4.6 mm; 2.6 μm) at 20 °C using acetonitrile-formic acid (pH 3.2; 1.0 mmol L-1) (92:08, v/v) at a flow rate of 0.8 mL/min. The compounds were monitored at 243 nm and the total time of analysis was 45 min. The method was validated in accordance with the current ICH guidelines for determination of impurities which include selectivity, linearity, accuracy, precision, limits of quantification and detection and robustness. The limits of quantification (LOQ) were 0.479; 0.0606 and 0.133 μg/mL for the impurities C, D and E, respectively. Furthermore, the validated methods were tested in iodixanol samples. The test results of the analyses of impurities and assay in those samples are presented and discussed accordingly.Este trabalho descreve pela primeira vez um método isocrático em uma única corrida analítica para quantificação das impurezas deacetil iodixanol (iodixanol composto relacionado C), iopentol (iodixanol composto relacionado D) e iodixanol ciclizado (iodixanol composto relacionado E) na matéria-prima iodixanol. Iodixanol é um composto dímerico, não-iônico, solúvel em água, usado para contraste para raios X com administração intravascular. As impurezas A e B não foram avaliadas neste trabalho, uma vez que não existem padrões disponíveis comercialmente dos mesmos. O método também foi validado para a quantificação de teor, uma vez que não existe método cromatográfico descrito no compêndio atual da USP para o teor. Estas impurezas podem ser formadas durante a síntese do iodixanol, e a importância da quantificação destas está relacionada à toxicidade. Neste trabalho foram avaliados os modos de eluição reverso e por interação hidrofílica (HILIC). O modo HILIC foi o selecionado, pois ofereceu boa eficiência cromatográfica com boa seletividade. Em ambos os modos, o uso de colunas de tecnologia fused-core foi empregado, por apresentar alta eficiência devido à sua melhor transferência de massa em comparação com as colunas analíticas convencionais. A separação cromatográfica foi conduzida utilizando-se a coluna analítica kinetex® HILIC (150 x 4,6 mm; 2,6 μm) a 20 °C e acetonitrila ácido fórmico (pH 3,2; 1,0 mmol L-1) (92:08, v/v) com 0,8 mL/min de vazão. Os compostos foram monitorados a 243 nm e o tempo total de análise foi de 45 min. Os métodos foram validados em acordo com as recomendações atuais do ICH para a determinação de impurezas, nas quais incluem seletividade, linearidade, exatidão, precisão, limites de quantificação e de detecção, e robustez. Os limites de quantificação foram de 0,479; 0,0606 e 0,133 μg/mL para as impurezas C, D e E, respectivamente. Deste modo, os métodos validados foram aplicados em amostras de iodixanol. Os resultados para a análise de impurezas e teor nestas amostras são, portanto, apresentados e discutidos.application/pdfporUniversidade Federal de São CarlosPrograma de Pós-Graduação de Mestrado Profissional em Química - PPGQUFSCarBRCromatografia líquidaIodixanolOrtogonalidadeHILICNúcleo fundidoCIENCIAS EXATAS E DA TERRA::QUIMICADesenvolvimento de método analítico por cromatografia líquida para determinação de impurezas no iodixanolAnalytical method development by high performace liquid chromatography for determination of impurities in iodixanolinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINAL5597.pdfapplication/pdf3304343https://{{ getenv "DSPACE_HOST" "repositorio.ufscar.br" }}/bitstream/ufscar/6653/1/5597.pdf0c450aff960d822ff2236d773f596f7fMD51TEXT5597.pdf.txt5597.pdf.txtExtracted texttext/plain0https://{{ getenv "DSPACE_HOST" "repositorio.ufscar.br" }}/bitstream/ufscar/6653/4/5597.pdf.txtd41d8cd98f00b204e9800998ecf8427eMD54THUMBNAIL5597.pdf.jpg5597.pdf.jpgIM Thumbnailimage/jpeg9885https://{{ getenv "DSPACE_HOST" "repositorio.ufscar.br" }}/bitstream/ufscar/6653/5/5597.pdf.jpga1f97c342ed1b7ebeaba591cab4a9633MD55ufscar/66532020-03-23 19:55:18.201oai:repositorio.ufscar.br:ufscar/6653Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-05-25T12:51:33.957569Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false |
dc.title.por.fl_str_mv |
Desenvolvimento de método analítico por cromatografia líquida para determinação de impurezas no iodixanol |
dc.title.alternative.eng.fl_str_mv |
Analytical method development by high performace liquid chromatography for determination of impurities in iodixanol |
title |
Desenvolvimento de método analítico por cromatografia líquida para determinação de impurezas no iodixanol |
spellingShingle |
Desenvolvimento de método analítico por cromatografia líquida para determinação de impurezas no iodixanol Rondon, Bruno Doratioto Cromatografia líquida Iodixanol Ortogonalidade HILIC Núcleo fundido CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
Desenvolvimento de método analítico por cromatografia líquida para determinação de impurezas no iodixanol |
title_full |
Desenvolvimento de método analítico por cromatografia líquida para determinação de impurezas no iodixanol |
title_fullStr |
Desenvolvimento de método analítico por cromatografia líquida para determinação de impurezas no iodixanol |
title_full_unstemmed |
Desenvolvimento de método analítico por cromatografia líquida para determinação de impurezas no iodixanol |
title_sort |
Desenvolvimento de método analítico por cromatografia líquida para determinação de impurezas no iodixanol |
author |
Rondon, Bruno Doratioto |
author_facet |
Rondon, Bruno Doratioto |
author_role |
author |
dc.contributor.author.fl_str_mv |
Rondon, Bruno Doratioto |
dc.contributor.advisor1.fl_str_mv |
Cass, Quezia Bezerra |
dc.contributor.advisor1Lattes.fl_str_mv |
http://genos.cnpq.br:12010/dwlattes/owa/prc_imp_cv_int?f_cod=K4781559E6 |
contributor_str_mv |
Cass, Quezia Bezerra |
dc.subject.por.fl_str_mv |
Cromatografia líquida Iodixanol Ortogonalidade HILIC Núcleo fundido |
topic |
Cromatografia líquida Iodixanol Ortogonalidade HILIC Núcleo fundido CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.cnpq.fl_str_mv |
CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
This work describes for the first time an isocratic method in a single analytical run to quantify deacetyl iodixanol (iodixanol related compound C), iopentol (iodixanol related compound D) and cyclized iodixanol (iodixanol related compound E), as impurities in iodixanol. Iodixanol is a drug substance, dimeric, nonionic, water-soluble, used as a radiographic contrast medium, which is administered by intravascular injection. The impurities A and B were not evaluated in this work, since they are not commercially available as standards. The method was also validated for the quantitative assay, since there is no chromatographic method described in the current USP compendium for the assay. The impurities can be formed during the synthesis process of iodixanol, and it is important to quantify them due to their related toxicity. In this work, the reverse and hydrophilic interaction (HILIC) modes of elution were evaluated. The hydrophilic elution mode was selected due to good efficiency and selectivity. In both modes of elution, columns having the technology fused-core were used, since they demonstrate high efficiency due to their better mass transfer in comparison to conventional HPLC columns. The chromatographic separation was carried out on a kinetex® HILIC column (150 x 4.6 mm; 2.6 μm) at 20 °C using acetonitrile-formic acid (pH 3.2; 1.0 mmol L-1) (92:08, v/v) at a flow rate of 0.8 mL/min. The compounds were monitored at 243 nm and the total time of analysis was 45 min. The method was validated in accordance with the current ICH guidelines for determination of impurities which include selectivity, linearity, accuracy, precision, limits of quantification and detection and robustness. The limits of quantification (LOQ) were 0.479; 0.0606 and 0.133 μg/mL for the impurities C, D and E, respectively. Furthermore, the validated methods were tested in iodixanol samples. The test results of the analyses of impurities and assay in those samples are presented and discussed accordingly. |
publishDate |
2013 |
dc.date.available.fl_str_mv |
2013-12-04 2016-06-02T20:37:48Z |
dc.date.issued.fl_str_mv |
2013-10-17 |
dc.date.accessioned.fl_str_mv |
2016-06-02T20:37:48Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
RONDON, Bruno Doratioto. Analytical method development by high performace liquid chromatography for determination of impurities in iodixanol. 2013. 97 f. Dissertação (Mestrado em Ciências Exatas e da Terra) - Universidade Federal de São Carlos, São Carlos, 2013. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufscar.br/handle/ufscar/6653 |
identifier_str_mv |
RONDON, Bruno Doratioto. Analytical method development by high performace liquid chromatography for determination of impurities in iodixanol. 2013. 97 f. Dissertação (Mestrado em Ciências Exatas e da Terra) - Universidade Federal de São Carlos, São Carlos, 2013. |
url |
https://repositorio.ufscar.br/handle/ufscar/6653 |
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por |
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openAccess |
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Universidade Federal de São Carlos |
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Programa de Pós-Graduação de Mestrado Profissional em Química - PPGQ |
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UFSCar |
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Universidade Federal de São Carlos |
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