LC–MS/MS and NMR Characterization of Key Impurities in Linagliptin and Pramipexole

Abstract

A sensitive, rugged, and robust LC-MS/MS and NMR analysis has been developed for the identification and characterization of key impurities of Linagliptin and Pramipexole. Linagliptin is used in the treatment of Type-2 diabetes. Linagliptin is a DPP-4 inhibitor which is an enzyme that degrades the incretin hormones (glucagon like peptide-1(GLP)) and glucose dependent insulinotropic polypeptide (GIP). Both these hormones increase insulin biosynthesis and secretion from pancreatic beta cells in the presence of normal and elevated blood glucose 20 levels. Pramipexole is a dopamine agonist of the non-ergoline class indicated for the treatment of Parkinson’s disease and restless legs Q1 syndrome. Parkinson’s disease is a neurodegenerative disease that affects the basal ganglia component, i.e., substantial nigra. Observed one of the key impurities in the analytical HPLC at around 1.30RRT in Lingliptin. To further characterize the impurity, the impurity was synthesized in presence of dibromo methane and was subjected to flash chromatography for further isolation. Thus isolated impurity was subjected to NMR and mass analysis for structure identification. Similarly observed another key impurity in Pramipexole at around 0.96RRT. This impurity was enriched in presence of formaldehyde and was subjected to preparative HPLC for isolation and further characterized by LC-MS and NMR.

Keywords:

• characterization
• isolation
• LC–MS/MS
• Linagliptin
• NMR
• pramipexole

Acknowledgment

The authors thank the management of Dr. Reddy’s Laboratories for supporting this work.