Degradation Pathway for Pitavastatin Calcium by Validated Stability Indicating UPLC Method

摘要

Degradation pathway for pitavastatin calcium is established as per ICH recommendations by validated and stability indicating reverse phase liquid chromatographic method. Pitavastatin is subjected to stress conditions of acid, base, oxidation, thermal and photolysis. Significant degradation is observed in acid and base stress conditions. Four impurities are studied among which impurity-4 is found prominent degradant. 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 BEH C18 stationary phase with simple mobile phase combination delivered in gradient mode and quantification is carried at 245 nm at a flow rate of 0.3 mL min-1. In the developed UPLC method the resolution between pitavastatin calcium and four potential impurities is found to be greater than 4.0. Regression analysis shows an r value (correlation coefficient) of greater than 0.998 for pitavastatin calcium and four potential impurities. This method is capable to detect the impurities of pitavastatin calcium at a level of 0.006% with respect to test concentration of 0.10 mg/mL for a 2-μL injection volume. The developed UPLC method is validated with respect to specificity, linearity & range, accuracy, precision and robustness for impurities determination and assay determination.