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Updated: Jan 23, 2026

Sample Preparation for Probe Electrospray Ionization Mass Spectrometry
Published on: February 19, 2020
A Novel 1,3-Sigmatropic Rearrangement in an Iminium Ion Generated in Collision-Induced Decomposition During
Wenbin Chen1, Jiangbo Xi1, Zhiyuan Gao2
1School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan, China.
Rationale:
Rapid structural elucidation of unknown pharmaceutical impurities is critical throughout the whole life cycle of drug development. It can be achieved by using multistage mass spectrometric analysis, in conjunction with the understanding of dissociation mechanisms of the ions generated by electrospray ionization.
Methods:
Liquid chromatography-UV/photo diode array detection-high resolution multistage mass spectrometric analysis (HiRes MSn) was used to elucidate the structure of an impurity of silodosin. The structure was confirmed by 1D and 2D NMR spectroscopy.
Results:
The impurity is identified as N-cyanomethylsilodosin, a solution degradant of silodosin. A novel 1,3-sigmatropic rearrangement was observed during one of its MS3 dissociation pathways. A mechanism is proposed for the 1,3-sigmatropic rearrangement, which is supported by the MSn behavior of a 13C-isotope labeled derivative of N-cyanomethylsilodosin.
Conclusion:
Elucidation of such an intra-molecular rearrangement mechanism not only enriches our understanding of the gas phase dissociation chemistry, but also should facilitate future rapid structural characterization of unknown pharmaceutical impurities and metabolites using multistage mass spectrometric analysis.
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