Isolation and Characterization of Novel Process-Related Impurities in Empagliflozin.

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.