RESUMO
In this work, a liquid chromatography stability-indicating method was developed and applied to study the hydrolytic behavior of simvastatin in different pH values and temperatures. The selected chromatographic conditions were a C18 column; acetonitrile-28 mM phosphate buffer solution, pH 4 (65 + 35) as the mobile phase; 251 degrees C column temperature; and flow rate 1 mL/min. The developed method exhibited an adequate repeatability and reproducibility (coefficient of variation 0.54 and 0.74%, respectively) and a recovery higher than 98%. Furthermore, the detection and quantification limits were 9.1 x 10(-7) and 2.8 x 10(-6) M, respectively. The degradation of simvastatin fitted to pseudo-first order kinetics. The degradation was pH dependent, being much higher at alkaline pH than at acid pH. Activation energy, kinetic rate constants (k) at different temperatures, the half life (t1/2) and the time for 10% degradation to occur (t90) values are also reported.
Assuntos
Técnicas de Química Analítica/métodos , Cromatografia Líquida/métodos , Sinvastatina/análise , Sinvastatina/química , Acetonitrilas/química , Soluções Tampão , Cromatografia , Cromatografia em Camada Fina , Concentração de Íons de Hidrogênio , Hidrólise , Inibidores de Hidroximetilglutaril-CoA Redutases/análise , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Cinética , Modelos Químicos , Fosfatos/química , Reprodutibilidade dos Testes , Temperatura , Fatores de TempoRESUMO
PURPOSE: To evaluate the reaction of a large series of pharmacologically significant 1,4-dihydropyridine (1,4-DHP) compounds with superoxide (O2.-) in dimethylsulfoxide using differential pulse voltammetry and controlled potential electrolysis. METHODS: Differential pulse voltammetry was used to track the consumption of O2.-, and controlled potential electrolysis was used to electrogenerate O2.-. RESULTS: With the addition of 1,4-DHP, the oxidation peak current of O2.- decreased concentration dependently, suggesting that 1,4-DHP reacts with O2.-, that is, 1,4-DHP scavenges O2.- in dimethylsulfoxide. CONCLUSIONS: very easy and direct voltammetric procedure to study the relative reactivity of different 1,4-DHP with O2.- is proposed. Using the proposed method we have found that all commercial 1,4-DHP reacts with O2.-. The following order of rates was obtained: felodipine > or = vitamin E > isradipine > nimodipine > furnidipine > nitrendipine > nisoldipine > nifedipine. Furthermore, it was demonstrated that the hydrogen at the N-position of 1,4-DHP compounds could be released as a proton in the presence of O2.-, thus the electrogenerated O2.- worked as a proton acceptor to 1,4-DHP.