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 ...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.展开更多
Background： Statins have proven efficacy in inhibiting the onset and progress of atherosclerosis. The effectiveness of pitavastatin in reversing carotid atherosclerosis associated with hypercholesterolemia （HC） is ...Background： Statins have proven efficacy in inhibiting the onset and progress of atherosclerosis. The effectiveness of pitavastatin in reversing carotid atherosclerosis associated with hypercholesterolemia （HC） is un-known. Objectives： To explore the simultaneous effects of pitavastatin calcium on brachial arterial flow-mediated vasodilatation （FMD）, carotid intima-media thickness （IMT）, and arterial stiffness （β）, three surrogate markers of ath-erosclerosis were studied in HC patients. Methods：A randomized, double-blind trial was performed with 40 HC sub-jects who fulfil ed the inclusion/exclusion criteria. Patients were given pitavastatin calcium 1 mg/d （Group 1） or 2 mg/d （Group 2） for 8 weeks. There were 20 patients in each group, and 30 gender-and age-matched healthy subjects as controls were recruited. FMD of the brachial artery, carotid IMT, and arterial stiffness indicated byβwere measured at baseline and at 8 weeks after starting pitavastatin calcium therapy using ultrasound techniques. Biochemical tests were also made on al subjects. Results： At baseline, higher total cholesterol （TC） and low-density lipoprotein cho-lesterol （LDL-C）, reduced FMD, and increasedβand IMT were observed in HC patients （P0.05）. Significant negative interactions between TC/LDL and FMD （P〈0.05–0.001）, positive interactions between TC and IMT （P=0.003） and between TC/LDL and β （P〈0.001–0.000） were found. Conclusions： Treatment with pitavastatin calcium exerted fa-vorable effects on endothelial function and arterial stiffness. It also improved carotid atherosclerosis in patients with HC.展开更多
文摘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.
基金Project supported by the National Science and Technology Major Project(No.2012ZX09303-016-003)the National Natural Science Foundation of China(Nos.81270352,81270287,81300168,81471036,and 81470560)
文摘Background： Statins have proven efficacy in inhibiting the onset and progress of atherosclerosis. The effectiveness of pitavastatin in reversing carotid atherosclerosis associated with hypercholesterolemia （HC） is un-known. Objectives： To explore the simultaneous effects of pitavastatin calcium on brachial arterial flow-mediated vasodilatation （FMD）, carotid intima-media thickness （IMT）, and arterial stiffness （β）, three surrogate markers of ath-erosclerosis were studied in HC patients. Methods：A randomized, double-blind trial was performed with 40 HC sub-jects who fulfil ed the inclusion/exclusion criteria. Patients were given pitavastatin calcium 1 mg/d （Group 1） or 2 mg/d （Group 2） for 8 weeks. There were 20 patients in each group, and 30 gender-and age-matched healthy subjects as controls were recruited. FMD of the brachial artery, carotid IMT, and arterial stiffness indicated byβwere measured at baseline and at 8 weeks after starting pitavastatin calcium therapy using ultrasound techniques. Biochemical tests were also made on al subjects. Results： At baseline, higher total cholesterol （TC） and low-density lipoprotein cho-lesterol （LDL-C）, reduced FMD, and increasedβand IMT were observed in HC patients （P0.05）. Significant negative interactions between TC/LDL and FMD （P〈0.05–0.001）, positive interactions between TC and IMT （P=0.003） and between TC/LDL and β （P〈0.001–0.000） were found. Conclusions： Treatment with pitavastatin calcium exerted fa-vorable effects on endothelial function and arterial stiffness. It also improved carotid atherosclerosis in patients with HC.
