DEVELOPMENT AND VALIDATION OF DEFERASIROX-RELATED SUBSTANCE METHOD IN SOLID DOSAGE FORMS USING HPLC

Objective: A simple, sensitive, and reproducible Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC) method was developed to quantitatively determine related substances in bulk and pharmaceutical dosage forms of Deferasirox (DFS). The method's performance was validated according to the present International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines for specificity, limit of detection (LOD), limit of quantification (LOQ), linearity, accuracy, precision, and Robustness. The developed method can be used for routine analysis of the determination of DFS in the presence of degradation products and impurities. Methods: Chromatographic separation was achieved on Shimadzu shim pack GIS (150*4.6) mm5µm using isocratic elution mode, which included 0.1 % Formic acid in Water: Acetonitrile in gradient mode as mobile phase at a flow rate of 1.0 ml/min. And column temperature of 40 °C. Detection was performed at a wavelength of 254 nm coupled with an Ultra Violet (UV) detector. The Injection volume was 10 µl. The drug was exposed to various stress conditions in degradation studies, such as acidic, basic, oxidative, hydrolytic, photolytic, and thermal degradation. Results: The retention time of DFS was 8.1 min. The resolution of DFS and four impurities was greater than 2.0 for all pairs of components. The high correlation coefficient (r2>0.9990) values indicated clear correlations between the investigated compound concentrations and their peak areas within the test ranges. The Repeatability and intermediate precision expressed by the Relative Standard Deviation (RSD) were less than 10%. The accuracy evaluated by performing recovery studies via a spike method was 50-150%. Stress Degradation studies were carried out; however, no significant degradation was observed in any of the stress degradation conditions, implying a chemically stable drug formulation and the method used to measure stability is robust to minor variations; hence, the product is likely to maintain its quality and efficacy throughout its shelf life. Conclusion: Hence, a suitable, reliable, accurate, precise, and economical HPLC method was developed, which is ideal for analyzing DFS in both bulk and commercial formulations.