title: Structural determination of the novel fragmentation routes of zwitteronic morphine opiate antagonists naloxonazine and naloxone hydrochlorides using electrospray ionization tandem mass spectrometry.
abstract: Electrospray ionization quadrupole time-of-flight (ESI-QqToF) mass spectra of the zwitteronic salts naloxonazine dihydrochloride 1 and naloxone hydrochloride 2, a common series of morphine opiate receptor antagonists, were recorded using different declustering potentials. The singly charged ion [M+H-2HCl](+) at m/z 651.3170 and the doubly charged ion [M+2H-2HCl](2+) at m/z 326.1700 were noted for naloxonazine dihydrochloride 1; and the singly charged ion [M+H-HCl](+) at m/z 328.1541 was observed for naloxone hydrochloride 2. Low-energy collision-induced dissociation tandem mass spectrometry (CID-MS/MS) experiments established the fragmentation routes of these compounds. In addition to the characteristic diagnostic product ions obtained, we noticed the formation of a series of radical product ions for the zwitteronic compounds 1 and 2, and also the formation of a distonic ion product formed from the singly charged ion [M+H-HCl](+) of naloxone hydrochloride 2. Confirmation of the various established fragmentation routes was effected by conducting a series of ESI-CID-QqTof-MS/MS product ion scans, which were initiated by CID in the atmospheric pressure/vacuum interface using a higher declustering potential. Deuterium labeling was also performed on the zwitteronic salts 1 and 2, in which the hydrogen atoms of the OH and NH groups were exchanged with deuterium atoms. Low-energy CID-QqTof-MS/MS product ion scans of the singly charged and doubly charged deuteriated molecules confirmed the initial fragmentation patterns proposed for the protonated molecules. Precursor ion scan analyses were also performed with a conventional quadrupole-hexapole-quadrupole tandem mass spectrometer and allowed the confirmation of the genesis of some diagnostic ions.
authors.affiliation: Laboratoire de Physico-Chimie des Interfaces et Applications FRE CNRS 2485, Fédération Chevreul FR CNRS 2638, Site de Béthune, IUT de Béthune BP819, 62408 Béthune, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Joly
authors.forename: Celine
authors.initials: C
authors.lastname: Vaillant
authors.forename: Alejandro M
authors.initials: AM
authors.lastname: Cohen
authors.forename: Patrick
authors.initials: P
authors.lastname: Martin
authors.forename: Mokhtar
authors.initials: M
authors.lastname: El Essassi
authors.forename: Mohamed
authors.initials: M
authors.lastname: Massoui
authors.forename: Joseph
authors.initials: J
authors.lastname: Banoub
mesh_terms: D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D009020:Morphine / Q000037:antagonists & inhibitors*; D009270:Naloxone / Q000031:analogs & derivatives* / Q000737:chemistry*; D018847:Opioid Peptides / Q000037:antagonists & inhibitors; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D018847:Opioid Peptides; D009270:Naloxone; D009020:Morphine; C034643:naloxonazine