Novel tandem hydrogen migrations across five chemical bonds for 1,4-dihydropyridine using electrospray ionization FT-ICR mass spectrometry

•1,4-dihydropyridines as a series of important target drugs were successfully analyzed using collision-induced dissociation (CID) method by ESI FT-ICR MS.•An intra-molecular tandem hydrogen migration by crossing five chemical bonds with a gas phase Na+/H+ exchange were observed.•The rearrangement mechanisms and key product ions were confirmed by high resolution tandem mass spectrometry and in solution deuterium labeling.•These characteristic fragmentation pathways are very helpful to interpret the basic chemistry of labile hydrogen atom in gas phase.

The electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FT-ICR MS) was applied to investigate the characteristic fragmentation patterns of 1, 4-dihydropyridines using collision-induced dissociation (CID) method in positive ion mode. The intra-molecular tandem hydrogen atom migrations were observed with gas phase Na+/H+ exchange by crossing five chemical bonds for 1,4-dihydropyridines. The possible rearrangement mechanisms were proposed for the first time, and the key structure of product ions were confirmed by high resolution tandem mass spectrometry and in solution hydrogen/deuterium labeling. The novel tandem hydrogen migration could be considered as a general fragmentation pattern for 1,4-dihydropyridine drugs because of their intrinsic chemical structures.

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