%0 Journal Article
%T Degradation Pathway for Eplerenone by Validated Stability Indicating UP-LC Method
%A Kondru Sudhakar Babu
%A Venkataramanna Madireddy
%A Venkata Somaraju Indukuri
%J ISRN Pharmaceutics
%D 2012
%R 10.5402/2012/251247
%X Degradation pathway for eplerenone is established as per ICH recommendations by validated and stability-indicating reverse phase liquid chromatographic method. Eplerenone is subjected to stress conditions of acid, base, oxidation, and thermal and photolysis. Significant degradation is observed in acid and base stress conditions. Four impurities are studied and the major degradant (RRT about 0.31) was identified by LC-MS and spectral analysis. The stress samples are assayed against a qualified reference standard and the mass balance is found close to 99.5%. Efficient chromatographic separation is achieved on a Waters symmetry C18 stationary phase with simple mobile phase combination delivered in gradient mode and quantification is carried at 240£¿nm at a flow rate of 1.0£¿mL£¿min£¿1. In the developed LC method the resolution between eplerenone and four potential impurities (imp-1, imp-2, imp-3, and imp-4) is found to be greater than 4.0. Regression analysis shows an value (correlation coefficient) of greater than 0.999 for eplerenone and four potential impurities. This method is capable to detect the impurities of eplerenone at a level of 0.020% with respect to test concentration of 1.0£¿mg£¿mL£¿1 for a 20£¿¦ÌL injection volume. The developed UPLC method is validated with respect to specificity, linearity and range, accuracy, precision, and robustness for impurities and assay determination. 1. Introduction Eplerenone, pregn-4-ene-7, 21-dicarboxylic acid, 9, 11-epoxy-17-hydroxy-3-oxo, ¦Ã-lactone, methyl ester (7¦Á, 11¦Á, 17¦Á), is an aldosterone antagonist used as an adjunct in the management of chronic heart failure. It is similar to the diuretic spironolactone, though it may be more specific for the mineralocorticoid receptor. Eplerenone is used alone or in combination with other medications to treat high blood pressure. Eplerenone is in a class of medications called mineralocorticoid receptor antagonists. It works by blocking the action of aldosterone, a natural substance in the body that raises blood pressure. Eplerenone blocks the actions of the hormone aldosterone in the body. Aldosterone is important for the regulation of blood pressure. Eplerenone (other names include SC-66110, CGP-30083, and epoxymexrenone) is the first agent to block the mineralocorticoid receptor with a high degree of selectivity and is under development for human therapeutic use in the 4 treatment of hypertension and heart failure post myocardial infarction [1¨C5]. A few chromatographic methods have appeared in the literature for the quantification of eplerenone in using SPE-LC-MS/MS for
%U http://www.hindawi.com/journals/isrn.pharmaceutics/2012/251247/