Characterization of seven antihistamines, their N ‐oxides and related metabolites by fast atom bombardment mass spectrometry and fast atom bombardment tandem mass spectrometry

We have examined the synthetic N ‐oxides of five ethylenediamine‐type antihistamines using fast atom bombardment (FAB) mass spectrometry and FAB tandem mass spectrometry (MS/MS). Fragmentation of the protonated molecule in the normal and collisionally activated spectra appeared to be characteristic for this class of antihistamine N ‐oxide. Spectra were also acquired from an ethanolamine and a propylamine antihistamine N ‐oxide for comparison. These results were very similar to those obtained from biologically produced antihistamine N ‐oxides, as well as isomeric metabolites, which were readily distinguished from the N ‐oxides by characteristic fragmentation. In addition, a prominent ion 16 daltons lower in mass, which has been attributed to loss of elemental oxygen from the protonated N ‐oxide in chemical ionization mass spectral studies, was shown to be a matrix‐dependent product of the solution‐phase reduction of the antihistamine N ‐oxide to the parent antihistamine during FAB ionization. These results demonstrate that with a non‐reducing matrix such as glycerol, FAB mass spectrometry and FAB MS/MS are excellent methods for the characterization of the non‐conjugated antihistamine metabolites such as the N ‐oxides.