Isolation and characterization of pseudo degradation products of acalabrutinib using ESI-HRMS/MS and NMR: Formation of possible geometrical isomers

A forced degradation study of acalabrutinib (ACB), used to treat relapsed mantle cell lymphoma, was performed to identify and characterize all possible major degradation products formed under different stress conditions. The degradation products (DP) were separated using reverse phase UHPLC system o...

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Published in:Journal of pharmaceutical and biomedical analysis 2023-02, Vol.225, p.115214-115214, Article 115214
Main Authors: Panda, Samikshya, Das, Mitalee, Kandula, Ravikanth Reddy, Gajjela, Raju, Ravuri, Naga Durga Harish, Kumar, Hemantha, Kalamse, Shruti, Mathur, Arvind, Roy, Amrita, Bagadi, Muralidhararao
Format: Article
Language:English
Subjects:
Acalabrutinib
Characterization
Chromatography, High Pressure Liquid
Degradation pathways
Drug Stability
ESI-HRMS/MS
Forced degradation
Hydrolysis
Isolation
Magnetic Resonance Spectroscopy
NMR
Oxidation-Reduction
Photolysis
Spectrometry, Mass, Electrospray Ionization
Tandem Mass Spectrometry
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Summary:A forced degradation study of acalabrutinib (ACB), used to treat relapsed mantle cell lymphoma, was performed to identify and characterize all possible major degradation products formed under different stress conditions. The degradation products (DP) were separated using reverse phase UHPLC system on Kinetex EVO C18 column. Major DPs formed were isolated using semi-preparative HPLC and characterized by LC-ESI-HRMS/MS and NMR. ACB degraded to form seven major degradants (DP-I to DP-VII). DP-I and DP-V were formed under alkaline stress condition, whereas DP-II, DP-III, DP-VI and DP-VII were formed under both acidic and basic conditions. Further, DP-IV was formed when ACB drug was exposed to hydrogen peroxide stress condition. ACB was found to be stable when subjected to aqueous (neutral pH), thermal and UV radiation of 254 nm, as it has not shown any significant degradation under these conditions. Interestingly, two pairs of pseudo geometrical isomeric DPs (DP-II and DP-III, DP-VI and DP-VII) were observed. The plausible degradation pathway of ACB and fragmentation patterns of both ACB and major DPs were discussed. •In the present work, two pairs of pseudo degradation products (DPs) of ACB were identified and characterized.•UHPLC-PDA method was developed to separate seven major DPs.•Seven DPs were isolated and characterized based on ESI-HRMS/MS and NMR experiments.•Degradation pathways of ACB were proposed and discussed.
ISSN:0731-7085
1873-264X
DOI:10.1016/j.jpba.2022.115214