Development and validation of a novel stability indicating RP-HPLC method for estimation of related substances and degradation products in Tolvaptana?°

摘要

A reverse phase liquid chromatographic (RP-LC) method was developed for the quantification of the related impurities of Tolvaptan drug substance. The method was optimized using buffer (prepared by dissolving 1.0mL H3PO4 (85%) taken in 1000mL milli-Q-water) taken as mobilephase-A, and Acetonitrile: Methanol in the ratio of 80:20 v/v as mobile phase-B. The flow rate was set at 1.2 mL min-1, wavelength at 240nm respectively and the column temperature was maintained at 35°C. The capability of stability indicating method developed was demonstrated by studying the degradation products generated during the forced degradation studies under the following conditions i) water hydrolysis, ii) at 75% relative humidity, iii) oxidative, iv) thermal v) photolytic, vi) acid, vii) base, and viii) photolytic degradation. The developed method can be used for the determination of synthetic and degradation impurities in the regular quality control analysis for the drug substance.