HPLC method with correction factor for determination of related substances in compound ezetimibe and rosuvastatin calcium tablets / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish the self contrast and correction factor method for the content determination of the related substances in compound ezetimibe and rosuvastatin calcium tablets simultaneously. METHODS: RP-HPLC method was adopted. The determination was performed on Kromasil 100-5 C18 Dimensions column (4.6 mm × 250 mm, 5 μm) with mobile phase A consisting of methanol-acetonitrile-0.05 mol·L-1 potassium dihydrogen phosphate (adjusted to pH 4.0 with phosphoric acid) (103060) and mobile phase B consisting of tetrahydrofuran-acetonitrile-0.05 mol·L-1 potassium dihydrogen phosphate (adjusted to pH 4.0 with phosphoric acid) (105040) at a flow rate of 1.0 mL·min-1. The detection wavelength was set at 242 nm. The injection volume was 20 μl. The slope of linear equation was used to determine the correction factors between ROS impurities 1, 2, 3, EZT impurities 1, 2, 3, 4, 5, 6, 7 and ezetimibe or rosuvastatin calcium. The relative retention time was used to determine the positions of impurities. RESULTS: The relative retention time of ROS impurities 1, 2, 3, 4 and EZT impurities 1, 2, 3, 4, 5, 6, 7 to rosuvastatin calcium was 1.5, 1.9, 2.1, 1.1, 1.7, 2.5, 2.6, 2.8, 2.9, 3.0, and 4.0, respectively. The correction factors of ROS impurities 1, 2, 3, 4 and EZT impurities 1, 2, 3, 4, 5, 6, 7 were 1.1, 1.1, 1.0, 1.0, 1.3, 1.1, 1.0, 1.3, 1.4, 0.5, and 1.0, respectively. The content of ROS impurity 4 was 0.15% in three batches of samples, the other impurities were less than 0.1%, and the contents of total impurities were 0.27%, 0.27%, and 0.26%, respectively. CONCLUSION: The method is simple, efficient, and accurate for analyzing the related substances in compound ezetimibe and rosuvastatin calcium tablets.