Abstract

ANALYTICAL METHOD DEVELOPMENT AND QUANTIFICATION OF GENOTOXIC AND CARCINOGENIC IMPURITIES IN AMLODIPINE AND BENAZEPRIL HCL CAPSULE USING HYPHENATED TECHNIQUE

Kiran Pokharkar*, Dr. Deepak Pareek and Dr. Swarup Prabhune

ABSTRACT

This work discusses the development and validation of an analytical technique employing GC-MS in Selective Ionization Mode (SIM) for the detection of genotoxic and carcinogenic impurities, namely NEIPA, NDIPA, NDEA, and N-nitroso morpholine, in Amlodipine and Benazepral HCl capsules. With R² values higher than 0.99 for every target molecule, the approach shown outstanding linearity. Calculated as 0.672-0.678 mcg/g (LOD) and 2.037 mcg/g (LOQ), the limits of detection (LD) and quantification (LOQ) for NEIPA, NDIPA, NDEA, and N-Nitroso Morpholine were Under the analytes' retention durations (NEIPA: 3.054 min, NDIPA: 5.041 min, NDEA: 6.924 min, N-Nitroso Morpholine: 8.998 min), specificity tests revealed no interference from other solvents. Studies of accuracy found compound'recovery rates ranging from 95.96% to 101.05%. With %RSD values below 2%, the technique's accuracy was shown; system precision for NEIPA and NDIPA was 1.44% and method precision was 0.961% for NEIPA and 1.97% for NDIPA. Using ICH criteria, the created approach was verified and shown to be appropriate for regulatory compliance and regular pharmaceutical quality control.

Keywords: Genotoxic impurities, Carcinogenic impurities, Nitrosamines, Method validation, ICH guidelines, Pharmaceutical analysis, Quality control, etc.