SEPARATION AND QUANTIFICATION OF PROCESS RELATED IMPURITIES AND DIASTEREOMERS IN APREPITANT BULK DRUG SUBSTANCE

Abstract

A gradient reversed-phase liquid chromatographic (RP-LC) method has been developed and, subsequently, validated for the separation and quantification of diastereomers and process related impurities of Aprepitant. The separation was achieved on a Kromasil C18, 250 × 4.6 mm, 5 µm column using a mobile phase consisting of potassium dihydrogen phosphate buffer, pH adjusted to 2.5 with phosphoric acid, and acetonitrile under gradient conditions. The flow rate was maintained at 1.0 mL min−1 and UV detection was performed at 210 nm. The described method is linear over the range of LOQ to 2.25 µg mL−1 (150% of the specification limit). The percentage recovery of impurities in bulk drug sample was ranged from 96 to 105%. The method is precise and accurate with RSD (%) value less than 1.0% and the recovery of impurities were in the range of 94–102%. The developed method was validated with respect to linearity, accuracy, precision, robustness, and forced degradation studies prove the stability indicating power of the method.