A comprehensive degradation study and identification of key degradation products of omeprazole drug substance including its degradation pathways using LC-HRMS and NMR

Omeprazole is a proton pump inhibitor widely used to treat acid-induced inflammation and ulcers of the stomach. A comprehensive forced degradation study was conducted on Omeprazole (OMP) drug substance (per ICH guidelines) to generate and identify the chemical structures of key potential degradation products of OMP. Samples from a typical commercial batch of OMP drug substance was subjected to acidic, alkaline, oxidative, photolytic, and thermal stress conditions. Thirty-four degradation products were generated in the forced degraded samples of OMP which were adequately separated by an investigational reversed phase high performance liquid chromatography method. The degradation products were identified and characterized using liquid chromatography-high resolution mass spectrometry (LC-HRMS) technique. Accurate mass measurements and fragmentation patterns from tandem mass spectrometry were used to propose molecular structure of degradation products. One major degradation product was isolated and purified by preparative liquid chromatography and the purified sample was analyzed by NMR for structure confirmation. The proposed chemical structures and possible degradation pathways were justified through mechanistic explanations. The information provided in this article facilitates better understanding of the stability of OMP drug substance under a wide range of conditions.