Collision-induced dissociation of protonated fentanyl: A DFT study

Abstract

The fragmentation pathways leading to the major products resulting from collision-induced dissociation of protonated fentanyl are investigated. Starting from a protonated fentanyl in a twist conformation, transfer of the proton from the piperidine to the amide nitrogen allows the lone pair of the piperidine nitrogen to assist in displacement of the amide group and results in ring-opening of the piperidine to yield an ion with m/z 188 (C13H18N+). This is the fragmentation pathway with the lowest energy barrier; the barrier to the loss of the phenethyl group as a phenonium or 1-phenylethyl cation from the nitrogen in the piperidine ring is 64 kJ mol−1 higher in energy. At even higher collision energies a bicyclic ion, also with nominal m/z 188 but with different elemental composition (C12H14NO+), is formed after sequential losses of ethene and phenethylamine from protonated fentanyl. Possible pathways to ring opening of the piperidine ring of N-protonated fentanyl include nucleophilic attack by the amide oxygen or the phenyl ring on the piperidine ring. The two m/z 188 ions give different dissociation products; minor products in the mass spectrum of protonated fentanyl at m/z 146, 134 and 132 are all generated from the dominant m/z 188 ion, C13H18N+, whereas only a product at m/z 132 is formed from the C12H14NO+ ion.