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Development, validation and clinical application of a HPLC-FL method for CYP2D6 phenotyping in South Brazilian breast cancer patients.
Antunes, Marina Venzon; Staudt, Dilana Elisabeth; Raymundo, Suziane; de Oliveira, Vanessa; Gössling, Gustavo; Pirolli, Rafaela; Biazús, Jorge Villanova; Cavalheiro, José Antônio; Rosa, Daniela Dornelles; Schwartsmann, Gilberto; Linden, Rafael.
Afiliación
  • Antunes MV; Pós-graduação em Ciências Médicas, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Instituto de Ciências da Saúde, Universidade Feevale, Novo Hamburgo, RS, Brazil. Electronic address: marinaantunes@feevale.br.
  • Staudt DE; Instituto de Ciências da Saúde, Universidade Feevale, Novo Hamburgo, RS, Brazil.
  • Raymundo S; Instituto de Ciências da Saúde, Universidade Feevale, Novo Hamburgo, RS, Brazil.
  • de Oliveira V; Instituto de Ciências da Saúde, Universidade Feevale, Novo Hamburgo, RS, Brazil.
  • Gössling G; Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
  • Pirolli R; Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
  • Biazús JV; Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
  • Cavalheiro JA; Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
  • Rosa DD; Hospital Moinhos de Vento, Porto Alegre, RS, Brazil.
  • Schwartsmann G; Pós-graduação em Ciências Médicas, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
  • Linden R; Instituto de Ciências da Saúde, Universidade Feevale, Novo Hamburgo, RS, Brazil.
Clin Biochem ; 47(12): 1084-90, 2014 Aug.
Article en En | MEDLINE | ID: mdl-24747158
OBJECTIVE: To develop and validate a method for determination of dextromethorphan (DMT) and dextrorphan (DTP) in plasma samples using HPLC-FL and to apply it to CYP2D6 phenotyping of a population from the South of Brazil. METHODS: Samples were prepared by hydrolysis and liquid-liquid extraction. Analysis was conducted in a reversed phase column, with isocratic elution and fluorescence detection. One hundred and forty patients being treated with tamoxifen were given 30 mg of dextromethorphan and their CYP2D6 phenotypes were determined on the basis of [DMT]/[DTP] metabolic ratios in plasma samples collected after 3h. RESULTS: Total chromatography running time was 12 min. Precision (CV%) was below 9.7% and accuracy was between 92.1 and 106.9%. The lower limits of quantification were 1 ng mL(-1) for DMT and 10 ng mL(-1) for DTP. Mean extraction yield of analytes was 86.6%. Mean age of patients was 55.7 years. Phenotype frequencies were as follows: 7.1% poor metabolizers, 13.6% intermediate metabolizers, 77.1% extensive metabolizers and 2.1 ultra-rapid metabolizers. Metabolic ratios for patients on strong (n=11) and weak (n=16) CYP2D6 activity inhibitors were different from each other and also different from ratios for patients not taking enzyme inhibitors (n=113). CONCLUSIONS: A sensitive method for determination of dextromethorphan and its metabolite in plasma samples was developed and successfully applied, providing evidence of the impact that CYP2D6 inhibitors have on the enzyme's metabolic capacity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Cromatografía Líquida de Alta Presión / Citocromo P-450 CYP2D6 Límite: Female / Humans País/Región como asunto: America do sul / Brasil Idioma: En Revista: Clin Biochem Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Cromatografía Líquida de Alta Presión / Citocromo P-450 CYP2D6 Límite: Female / Humans País/Región como asunto: America do sul / Brasil Idioma: En Revista: Clin Biochem Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos