Electron-Induced Dissociation of Singly Charged Organic Cations as a Tool for Structural Characterization of Pharmaceutical Type Molecules

Abstract

Collision-induced dissociation (CID) and electron-induced dissociation (EID) have been investigated for a selection of small, singly charged organic molecules of pharmaceutical interest. Comparison of these techniques has shown that EID carried out on an FTICR MS and CID performed on a linear ion trap MS produce complementary data. In a study of 33 molecule-cations, EID generated over 300 product ions compared to 190 product ions by CID with an average of only 3 product ions per precursor ion common to both tandem MS techniques. Even multiple stages of CID failed to generate many of the product ions observed following EID. The charge carrying species is also shown to have a very significant effect on the degree of fragmentation and types of product ion resulting from EID. Protonated species behave much like the ammonium adduct with suggestion of a hydrogen atom from the charge carrying species strongly affecting the fragmentation mechanism. Sodium and potassium are retained by nearly every product ion formed from [M + Na](+) or [M + K](+) and provide information to complement the EID of [M + H](+) or [M + NH(4)](+). In summary, EID is proven to be a fitting partner to CID in the structural elucidation of small singly charged ions and by studying EID of a molecule-ion holding different charge carrying species, an even greater depth of detail can be obtained for functional groups commonly used in synthetic chemistry.

Differentiating Fragmentation Pathways of Cholesterol by Two-Dimensional Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

“…2D FT-ICR MS can also be adapted to other fragmentation methods for small molecules, such as electroninduced dissociation (EID) [56,57].…”

Fragmentation patterns of boron‐dipyrromethene (BODIPY) dyes by electrospray ionization high‐resolution tandem mass spectrometry

“…In recent years, ion‐electron dissociation techniques have been increasingly applied to study the structure of small molecules, as activation of radical ions usually leads to extensive cleavages and provides more structural information . However, due to the extremely low fragmentation efficiency compared with CID, ion‐electron dissociation techniques are not commonly applied in routine structural elucidation experiments.…”

Electron-Induced Dissociation of Peptides in a Triple Quadrupole Mass Spectrometer Retrofitted with an Electromagnetostatic Cell

“…Efforts by the present authors are underway to eliminate this shortcoming in the EMS cell. Assuming this is accomplished, EMS cells incorporated into QqQ or QqTOF mass spectrometers would make tandem high-energy EID mass spectrometry more widely accessible for analyses of peptides and small, singly charged molecules like pharmaceuticals [42–45]. Q[EMS]qQ platforms would make possible targeted multiple reaction monitoring (MRM) of peptides based on EID transitions or combined EID/CID transitions, a capability that could have widespread applicability in pharmaceutical and clinical analyses.…”