DEVELOPMENT OF STABILITY – INDICATING HPLC METHOD FOR SIMULTANEOUS DETERMINATION OF THIRTEEN RELATED IMPURITIES IN NINTEDANIB ESYLATE DRUG SUBSTANCE & ITS APPLICATION IN DRUG PRODUCT

A stability indicating reverse phase high-performance liquid chromatography (RP‑HPLC) method was developed and validated for the determination of thirteen related impurities in Nintedanib esylate, applicable to both bulk drug and finished product. Chromatographic separation was achieved on a Waters X‑Bridge C18 column (250 mm × 4.6 mm i.d., 5 µm) under gradient elution. The mobile phase consisted of 0.01 M ammonium bicarbonate buffer (pH 8.0 ± 0.05, adjusted with sodium hydroxide) as phase A, and a mixture of methanol, acetonitrile, and buffer (45:45:10, v/v) as phase B. Detection was performed at 240 nm, ensuring baseline resolution of Nintedanib from its impurities, with peak resolution consistently greater than 2. Forced degradation studies under acidic, alkaline, aqueous hydrolysis, and oxidative conditions confirmed the method’s ability to separate Nintedanib from its degradation products, including the major related substance (RS9). The method was validated in accordance with ICH guidelines for selectivity, linearity, accuracy, precision, and solution stability. This validated RP‑HPLC method provides a robust and reliable approach for routine analysis of related impurities in Nintedanib esylate drug substance and drug product, supporting quality control and stability assessment in pharmaceutical development and manufacturing.