Desenvolvimento e validação de metodologia analítica para a determinação de mebendazol em formas farmacêuticas por cromatografia líquida de alta eficiência e estudo de estabilidade

Abstract

The development and validation of analytical methodology indicative of stability is an essential item for the registration and marketing of pharmaceuticals. Mebendazole, an anthelmintic belonging to the group of benzimidazole that acts to inhibit glucose uptake by the worms, thus reducing their time of survival and reproduction. In drugs, climatic factors are very important in the stability because this depends on environmental factors and factors related to the product itself. The analytical methods used in stability analyzes should be validated and be indicative of stability. These methods should be sensitive to the presence or to assess qualitative and quantitative formation of products and / or degradation products. It was developed and validated a methodology for the study of stability analyzes in pharmaceutical forms for mebendazole tablets 100 mg and 500 mg oral suspension and 20 mg / mL using mobile phase volatile aqueous solution pH 2.1 and acetonitrile (80:20) and C18 chromatographic column. Stressful situations used for stress and verification of degrading were oxidation, acid and base hydrolysis, light and moisture. The analytical methodology was developed subjected to validation tests and the results obtained demonstrated that the analytical technique is proposed selective, linear over the range studied (0.2 to 130%), sensitive, accurate, and robust for quantification of mebendazole in pharmaceutical forms studied, against small changes in the flow of mobile phase, temperature of the chromatographic column, batch and column types, pH and composition of the mobile phase and marks the filter membrane. Thus, it was possible to develop and validate a unique methodology for the study of stability in tablets and oral suspension mebendazole, 100 and 500 mg per tablet and 20 mg / mL, respectively. Results were obtained from about 7000 theoretical plates, relative standard deviation of 0.1% in suitability, linearity with correlation coefficient approximately 1, symmetry factor of approximately 1.1. Degradation with greater number of training degrading occurred in an oxid environment, but with greater intensity degradation in basic medium. In the robustness analysis , there were no variations exceeding 2 % in relation to the condition indicial method front flow variations in ± 0.1 mL / min, the temperature of the sample compartment within ± 5 °C, pH of the aqueous phase within ± 0.1, mobile phase ratio of 80:20 ( 77:23 and 83:17). The use of a single method was extremely useful for analyzing the behavior of mebendazole across the different matrices of the drug. This allowed a better evaluation of the results of degradation products front of the stressful conditions which can be used for the purpose of improving the final product.