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.
Lay
J O
JO
Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079.
Holder
C L
CL
Cooper
W M
WM
D004983:Ethanolamines / Q000032:analysis; D005029:Ethylenediamines / Q000032:analysis; D006634:Histamine H1 Antagonists / Q000032:analysis*; D007536:Isomerism; D013058:Mass Spectrometry; D011437:Propylamines / Q000032:analysis; D013997:Time Factors
D004983:Ethanolamines; D005029:Ethylenediamines; D006634:Histamine H1 Antagonists; D011437:Propylamines