Development and Validation of Stability-indicating High-Performance Liquid Chromatography Method for Estimation of Organic Impurities of Carvedilol from Bulk and its Dosage Form

Abstract

The United States Pharmacopeia monograph of carvedilol states 3 different methods for evaluation of organic impurities. The present study provides a single stability-indicating analytical method for estimation of carvedilol and its organic impurities from bulk and its tablets dosage forms. The method uses Purosphere STAR RP 18-endcapped (250×4 mm, 3 µm) column and a gradient elution with a flow of 1 ml/min. Mobile phase buffer was prepared by adding 1 ml of triethylamine solution to 20 mM potassium dihydrogen phosphate solution, and pH was adjusted to 2.8±0.05 with orthphosphoric acid. Mobile phase A comprises of acetonitrile:buffer (10:1000 v/v), whereas Mobile phase B consist of methanol:acetonitrile:buffer (500:400:150 v/v/v). The eluted compounds were monitored at 226 nm and 240 nm. The column oven temperature was maintained at 50°. In the current chromatographic method total 19 impurities (3 degradation and 16 process related impurities) of carvedilol were separated in a single run. The developed method was validated as per International Council for Harmonisation guidelines for various parameters like system suitability, linearity, precision, accuracy, sensitivity (limits of detection and limits of quantification) and force degradation. All the validation parameters were within the acceptable range. The developed and validated method was quantitatively applied for estimation of all the process and degradation impurities in carvedilol active pharmaceutical ingredient and tablet formulation.