A QUALITY BY DESIGN APPROACH FOR DEVELOPMENT OF SIMPLE AND ROBUST REVERSED PHASE STABILITY INDICATING HPLC METHOD FOR ESTIMATION OF IBRUTINIB AND ITS IMPURITIES

Novel stability-indicating quality by design-based reversed-phase HPLC method is developed for the determination of Ibrutinib capsules and its impurities. A column (X-Bridge-C18 150 x 4.6 mm, 3μm,) with the stable bond stationary phase and two different mobile phases A and B are used for effective separation of Ibrutinib and its impurities. All compounds are monitored using a Photo Diode Array detector at 220 nm. The developed technique is found to be vigorous within the distinct design space and the flow gradient has been optimized. Ibrutinib is degraded under various stress test conditions as per International Council for Harmonisation and the parameters namely; linearity, stability, specificity, accuracy, precision, limit of detection and limit of quantization are assessed. To achieve the limit of quantization values under the reporting threshold, injection volumes and test concentrations have been optimized. The developed methodology is successful and robust and supportive in the areas where regulatory agencies propose HPLC analytical techniques.