The fragmentation reactions of the MH ions of Leu-enkephalin amide and a variety of heptapeptide amides have been studied in detail as a function of collision energy using a QqToF beam type mass spectrometer. The initial fragmentation of the protonated amides involves primarily formation of b ions, including significant loss of NH from the MH ions. Further fragmentation of these b ions occurs following macrocyclization/ring opening leading in many cases to b ions with permuted sequences and, thus, to formation of non-direct sequence ions. The importance of these non-direct sequence ions increases markedly with increasing collision energy, making peptide sequence determination difficult, if not impossible, at higher collision energies. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]