TITLE:
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)
AUTHORS:
Arun D. Bhutnar, Seema R. Saple, Vikas V. Vaidya
KEYWORDS:
Osimertinib Mesylate (OSM), Base Degradation, Semi-Preparative Isolation and Characterizations by HPLC, UPLC-QTOF-MS/MS, NMR Techniques
JOURNAL NAME:
Advances in Biological Chemistry,
Vol.11 No.1,
February
2,
2021
ABSTRACT: 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 NexusTM,
and MultiCASE, Case UltraTM widely accepted and respected software’s for DP and
OSM.