Author(s)

Arun D. Bhutnar^1*, Seema R. Saple¹, Vikas V. Vaidya²

¹Department of Chemistry, Kirti M Doongursee College, Mumbai University, Mumbai, India.
²Royal college of Arts, Science and commerce, Mumbai University, Thane, India.

The present work encompasses identification and characterization of major degradation product (DP) of OSM observed in base hydrolytic stress study. The separation of DP was carried out on a non-polar stationary phase by using high-performance liquid chromatography system (HPLC). Using waters X-bridge (250 mm × 4.6 mm, 5 μm) C18 column with gradient elution program. For the characterization study, stress samples were subjected to HPLC and UPLC-QTOF-MS/MS and based on mass fragmentation pattern, plausible structure was deduced. Further, the DP was isolated using semi-prepara- tive liquid chromatography and concentrated the fractions using lyophilization. The isolated DP was subjected to extensive 1D (1H, 13C, and DEPT-135) and 2D (COSY, HSQC and HMBC) nuclear magnetic resonance (NMR) studies to authenticate the structure. The impurity was unambiguously named as N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-metho-xy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)-3-methoxypropanamide. Add- itionally, the In-Silico structure activity relation (QSAR) assessed through statistical based software’s DEREK Nexus^TM, and MultiCASE, Case Ultra^TM widely accepted and respected software’s for DP and OSM.

Osimertinib Mesylate (OSM), Base Degradation, Semi-Preparative Isolation and Characterizations by HPLC, UPLC-QTOF-MS/MS , NMR Techniques

Bhutnar, A. , Saple, S. and Vaidya, V. (2021) Separation, Identification, Isolation and Characterization of Degradation Product of Osimertinib Tablets by UPLC-QTOF-MS/MS and NMR: Evaluation of In-Silico Safety Assessment for Osimertinib (OSM) and Degradation Product (DP). Advances in Biological Chemistry, 11, 15-29. doi: 10.4236/abc.2021.111003.