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Characterization of degradation products of regorafenib by LC-QTOF-MS and NMR: Investigation of rearrangement and odd-electron ion formation during collision-induced dissociations under ESI-MS/MS

Abstract

Regorafenib is an oral multikinase inhibitor, was subjected to stress conditions (hydrolysis, oxidative, thermal and photolytic) as per ICH specified conditions. The drug showed considerable degradation under hydrolysis (acidic, basic and neutral) and oxidative stress conditions, whereas it was stable under other stress conditions. A total of five degradation products (DPs) were observed and these were analyzed by using UHPLC-DAD system. The chromatographic separation was achieved on an Acquity CSH C18 (100×2.1 mm, 1.7µ) column using 0.1% formic acid and acetonitrile: methanol (80: 20, %v/v) as mobile phase in gradient mode. All DPs were characterized by LC–MS/MS and major degradation product (DP1) was isolated by using preparative HPLC from degradation mixture and analyzed using NMR (1D and 2D NMR) and IR experiments. It was observed that protonated DP1 and DP3 undergo rearrangement reactions during collision induced dissociations under positive electrospray ionization conditions. Additionally, in silico toxicity of the drug and its degradation products (DP1-DP5) were evaluated using TOPKAT and DEREK toxicity prediction software tools.

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Publication details

The article was received on 09 May 2017, accepted on 01 Sep 2017 and first published on 05 Sep 2017


Article type: Paper
DOI: 10.1039/C7NJ01440F
Citation: New J. Chem., 2017, Accepted Manuscript
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    Characterization of degradation products of regorafenib by LC-QTOF-MS and NMR: Investigation of rearrangement and odd-electron ion formation during collision-induced dissociations under ESI-MS/MS

    S. M. Baira, S. Gannoju, R. D. Nimbalkar, P. Garg, S. R and M. V. N. K. Talluri, New J. Chem., 2017, Accepted Manuscript , DOI: 10.1039/C7NJ01440F

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