Otimização do método analítico para a separação simultânea do maleato de enalapril e impurezas orgânicas, em formulações farmacêuticas, por HPLC-UV

Abstract

Enalapril maleate tablets are commonly used in the treatment of hypertension because they reduce blood pressure by reversibly inhibiting angiotensin-converting enzyme. During the manufacturing process of the tablets, they are tested for physicochemical analyzes that attest to the quality of them. The procedures and specifications for the analysis of enalapril maleate are present in the 6th edition Brazilian Pharmacopoeia and, whitin the analyses, is the quantification of assay and impurities. For this analysis, the Pharmacopoeia provides a method by HPLC-UV, using a C8 column of 250 x 4,6 mm and mobile phase composed of acetonitrile and phosphate buffer pH 2,2 25:75. In this sense, the present work aims at optimizing the pharmacopeic analytical method in order to reduce the analysis time and the environmental generated impact, mainly by the use of organic solvent and generation of analytical residues. For this purpose, the chromatographic column was replaced by a C18 column of 100 x 4,6 mm and some mobile phase compositions were tested, replacing acetonitrile by ethanol and modifying the proportion of organic solvent and buffer. Finally, it was concluded that the composition that generated the best result was ethanol and phosphate buffer pH 2,2 in the proportion 30:70. The optimized method was compared with the Pharmacopoeia in relation to the environmental and safety impacts for the analyst using the NEMI, Eco-Scale and GAPI tools, obtaining favorable results for the optimized method in the three comparisons. Next, the ability of the optimized method to accurately quantify the enalapril content and its impurities in 5 and 10 mg tablets was demonstrated. The analytical validation proved to be selective, precise, accurate and robust, in accordance with the specifications contained in RDC Nº 166/17.