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Structural determination of the novel fragmentation routes of zwitteronic morphine opiate antagonists naloxonazine and naloxone hydrochlorides using electrospray ionization tandem mass spectrometry
Author(s) -
Joly Nicolas,
Vaillant Celine,
Cohen Alejandro M.,
Martin Patrick,
Essassi Mokhtar El,
Massoui Mohamed,
Banoub Joseph
Publication year - 2007
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.2935
Subject(s) - chemistry , tandem mass spectrometry , electrospray ionization , fragmentation (computing) , collision induced dissociation , electrospray , ion , mass spectrometry , molecule , dissociation (chemistry) , polyatomic ion , analytical chemistry (journal) , chromatography , organic chemistry , computer science , operating system
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+H2HCl] + at m/z 651.3170 and the doubly charged ion [M+2H2HCl] 2+ at m/z 326.1700 were noted for naloxonazine dihydrochloride 1 ; and the singly charged ion [M+HHCl] + 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+HHCl] + 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. Copyright © 2007 John Wiley & Sons, Ltd.