Development, validation and clinical application of a HPLC-FL method for CYP2D6 phenotyping in South Brazilian breast cancer patients
| Autor: | Suziane Raymundo, Jorge Villanova Biazús, Gustavo Gössling, José Antônio Crespo Cavalheiro, Vanessa de Oliveira, Gilberto Schwartsmann, Dilana Elisabeth Staudt, Rafael Linden, Rafaela Pirolli, Marina Venzon Antunes, Daniela Dornelles Rosa |
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| Rok vydání: | 2014 |
| Předmět: |
CYP2D6
Analyte Metabolite Clinical Biochemistry Population Breast Neoplasms High-performance liquid chromatography chemistry.chemical_compound Breast cancer Dextrorphan medicine Humans education Chromatography High Pressure Liquid education.field_of_study Chromatography General Medicine Dextromethorphan medicine.disease Antineoplastic Agents Phytogenic Tamoxifen Cytochrome P-450 CYP2D6 chemistry Female Brazil medicine.drug |
| Zdroj: | Clinical Biochemistry. 47:1084-1090 |
| ISSN: | 0009-9120 |
| DOI: | 10.1016/j.clinbiochem.2014.04.008 |
| Popis: | 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 3 h. 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. |
| Databáze: | OpenAIRE |
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