A NOVEL HPLC METHOD FOR ESTIMATION OF GENOTOXIC IMPURITY 3-ACETAMIDOBENZENE 1, 2 DICARBOXYLIC ACID IN A KEY STARTING MATERIAL 3-ACETAMIDOPTHALIC ANHYDRIDE OF APREMILAST API

摘要

3-Acetamidobenzene 1, 2 dicarboxylic acid is a potential genotoxic impurity which gets formed during synthesis of 3-Acetamidopthalic anhydride, a key starting material (KSM) for manufacturing of Apremi-last API. During handling upon exposure to moisture, the anhydride ring of KSM 3-Acetamidopthalic anhydride opens to form acid. Hence Reverse phase HPLC method is not a feasible and robust option for estimation of this impurity. To overcome these problems a Normal phase HPLC method is developed and proposed in this research work. Immobilized Chiral pack IA column from Daicel is used for estimation. n-Hexane and isopropyl alcohol in 90:10 (VA/) ratio modified with 0.1% trifluroacetic acid is used as Mobile phase. Method is validated as per ICH guidelines. Limit of Detection (LOD) and Limit of Quantification (LOQ) are found to be 0.47 ppm (0.0047%) and 1.42 ppm (0.0142%), respectively. The method is linear over LOQ to 150%. Recovery is within limit (80-120%). Method is robust for parameters like mobile phase composition, flow rate, wavelength changes and column oven temperature.