Obtenção e caracterização química e farmacocinética do produto de fotodegradação do nifedipino

• Autor(a) principal: Oliveira, Maysa Aparecida de
• Data de Publicação: 2013
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/8672
• topic: Método bioanalítico; HPLC-DAD; Nifedipino; Farmacocinética; Validação; Bioanalytical method; Nifedipine; Pharmacokinetics; Validation; CIENCIAS DA SAUDE::MEDICINA

A simple and accurate stability-indicating high-performance liquid chromatography (HPLC-DAD) method was developed to measure nifedipine (NIF) in plasma in the presence of its degradation products. The chromatographic separation was performed on a C18 column using H3PO4 0.01%:CH3CN:CH3OH (60:20:20, v/v/v) as the mobile phase and a 1.0ml/min flow rate. The analytical validation was performed according to FDA, EMA and ANVISA (Brazilian Health Surveillance Agency) guidelines and was linear between 100.0 and 2000.0 ng/ml, precise (1.9 to 11.3%) and accurate (86.0 to 113.1%). Under the evaluated conditions, NIF in plasma samples were stable after processing and freeze-thaw cycles. The average liquid-liquid extraction recovery was 101.3 ± 5.4%. After validation, this method was applied to evaluate the influence of nitrosophenylpyridine (NO-NIF) in the pharmacokinetic of NIF in plasma of Wistar rats. This method was also validated for quality control of NO-NIF obtained after photodegradation of NIF in photostability chamber. The method showed selectivity, linearity (0.4 to 2.4mg/ml), as well as precision and accuracy. Nitrophenylpyridine (NINIF) was synthesized from the NIF. These degradation products were characterized by NMR and mass spectroscopy. In addition, a breakdown product of NO-NIF due to its contact with plasma was identified and characterized.