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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