STRESS DEGRADATION BEHAVIOR OF PREGABALIN, IDENTIFICATION OF DEGRADATION IMPURITIES AND DEVELOPMENT OF STABILITY INDICATING UPLC METHOD

A novel, high-throughput, reverse phase-ultra performance liquid chromatographic (RP-UPLC) method has been developed for the quantification of Pregabalin and its related impurities in drug substance. The stability-indicating capability of the developed method is demonstrated using forced degradation samples from stress conditions such as hydrolysis, oxidation, thermal and photolytic degradation. The separation of known impurities and degradation impurities are accomplished using a phenyl-hexyl stationary phase with 100 mm length and 1.7 µm particle size in short run time (10 min). The developed method employs a linear gradient elution with phosphate buffer pH 6.2-acetonitrile as mobile phase, and is validated in accordance with International Conference on Harmonization requirements.  During forced degradation it has been observed significant degradation of drug substance in base hydrolysis and oxidative stress conditions, and slight degradation of drug substance in acid hydrolysis and thermal stress conditions. The ten major oxidative degradation impurities formed are identified by LC-MS, HR-MS and NMR techniques and the proposed structure are reported