Isolation and characterization of novel process-related impurities in empagliflozin
Yanqing Chen1, Huiliang Li1, Hang Hong1
1Key Laboratory of Chemical Biology and Traditional Chinese Medicine (Ministry of Educational of China), Key Laboratory of Phytochemistry R&D of Hunan Province, and Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan, 410081, China.
Abstract:
Empagliflozin is an effective sodium glucose cotransporter-2 (SGLT2) inhibitor to improve glycemic control in adults with type 2 diabetes. During the manufacture of empagliflozin, three unknown impurities were discovered in pilot batches ranging from 0.05 % to 0.15 % by LC analysis. These unknown impurities were isolated from the crystallization mother liquor by column chromatography and semi-preparative LC, and their structures were elucidated by comprehensive analysis of HRMS, 1D-NMR (1H, 13C) and 2D-NMR (1H-1H COSY, HSQC, HMBC) spectroscopy data. The plausible mechanistic pathways to the formation of these three impurities were also discussed.
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