Six ion fragmentation techniques that can distinguish aspartic acid from its 
isomer, isoaspartic acid, were compared. MALDI post-source decay (PSD), MALDI 
157 nm photodissociation, tris(2,4,6-trimethoxyphenyl)phosphonium bromide (TMPP) 
charge tagging in PSD and photodissociation, ESI collision-induced dissociation 
(CID), electron transfer dissociation (ETD), and free-radical initiated peptide 
sequencing (FRIPS) with CID were applied to peptides containing either aspartic 
or isoaspartic acid. Diagnostic ions, such as the y-46 and b+H2O, are present in 
PSD, photodissociation, and charge tagging. c•+57 and z-57 ions are observed in 
ETD and FRIPS experiments. For some molecules, aspartic and isoaspartic acid 
yield ion fragments with significantly different intensities. ETD and charge 
tagging appear to be most effective at distinguishing these residues. Graphical 
Abstract ᅟ.