A Combined MS/MS and IMS Study Into the Fragmentation Pathway of Nifedipine

Area of Science:

• Analytical Chemistry
• Organic Chemistry
• Computational Chemistry

Background:

• Collision-induced dissociation (CID) is crucial for identifying small molecules, but interpreting MS/MS spectra, especially radical loss from protonated molecules and sodium adducts, lacks mechanistic depth.
• Current methods often rely on literature comparison, with proposed structures lacking rigorous mechanistic justification and conclusive evidence.
• The even-electron rule and fragmentation pathways of sodium adduct ions require further exploration for accurate structural elucidation.

Purpose of the Study:

• To investigate and elucidate the mechanisms of radical loss from even-electron nitro-containing compounds using collision-induced dissociation (CID).
• To improve the understanding of fragmentation patterns in mass spectrometry/mass spectrometry (MS/MS) for enhanced structural identification.
• To explore the influence of the nitro group's position on fragmentation and introduce the concept of an 'ortho effect'.

Main Methods:

• Mechanistic study of fragmentation patterns of nifedipine, m-nifedipine, and related analogues using CID.
• Utilized isotope-labeled analogs, ion mobility spectrometry (IMS), precursor ion scan (PIS), and density functional theory (DFT) calculations.
• Combined ion mobility spectrometry (IMS) with MS/MS for detailed fragmentation pathway elucidation.

Main Results:

• Fragment ions from protonated ([M+H]+) and sodium adduct ([M+Na]+) molecules of nifedipine exhibited distinct mechanisms compared to positional isomers.
• Similar fragmentation patterns were observed between nifedipine and analogues like nisoldipine and aranidipine.
• The ortho-positioned nitro group was identified as a key factor influencing fragment stability, leading to a novel 'ortho effect' fragmentation mechanism.

Conclusions:

• The study successfully elucidated unique fragmentation mechanisms, including radical loss, in nitro-containing compounds.
• The 'ortho effect' provides a new mechanistic insight into the fragmentation of specific nitro-containing molecules.
• Combining IMS with MS/MS offers a powerful approach for deciphering complex fragmentation pathways in mass spectrometry.