Forced degradation of Ceritinib under stress conditions: Structural interpretation of novel degradants using HR-MS/MS and NMR. (2020)

• Record Type: Journal Article
• Authors: Vajjha, Soujanya; Bommuluri, Vijay; Rumalla, Chidananda Swamy; Kaliyaperumal, Muralidharan; Korupolu, Raghu Babu; chopella, Vidyasagar
• Is Part Of: Materials today. Volume 33:Part 5(2020)
• Page Start: 2067
• Page End: 2076
• Publication Date: 2020
• Subjects: Ceritinib -- Drug degradation -- Structural elucidation; Materials science -- Congresses -- Periodicals; 620.1
• DOI: 10.1016/j.matpr.2020.01.588
• Languages: English
• ISSNs: 2214-7853

Abstract

Highlights: Ceritinib was exposed to like acid, base, oxidation, thermal, photolytic stress conditions. Ceritinib is readily undergoing change in acid degradation. One novel acid degradation product (DP-1) was observed in acid condition. Structure of DP-1 was characterised by expansive analysis of HRMS and NMR spectral studies. Abstract: The current work describes the preparative isolation and structural interpretation of acid degradation product of ceritinib (CRB). The drug is exposed to different stress conditions (acid, base hydrolysis, oxidation, thermal and photolytic) as suggested by International Conference on Harmonisation guidelines (ICH). The degradation of drug (CRB) is observed when exposed to acidic condition whereas the drug is stable in remaining stress conditions. The separation between drug and acid degradant was attained on a C18 BEH UPLC column (50 mm × 2.1 mm, 1.7 μm) in a gradient separation mode. The mobile phase comprises of acetonitrile and 0.05% formic acid buffer at a flow rate of 0.6 mL/min and UV wavelength monitored at 215 nm. One novel degradation product formed in acidic condition was isolated by Preparative HPLC (Prep-HPLC). Structural interpretation and characterisation done by HR-MS/MS and NMR studies which is not yet described in the literature.