title: Fragmentation of N-oxides (deoxygenation) in atmospheric pressure ionization: investigation of the activation process.
abstract: The diagnostic fragmentation of N-oxides resulting from loss of the oxygen atom (MH+ --> MH+-O) in electrospray and atmospheric pressure chemical ionization (APCI) mass spectra was investigated. When the temperature of the heated capillary tube was elevated, the ratio of the intensity of the [MH+ -16] fragment to the precursor ion (MH+) increased. This 'deoxygenation' process was associated with thermal activation and did not result from collisional activation in the desolvation region of the API source. Although the extent of 'deoxygenation' is compound-dependent, it can provide evidence for the presence of an N-oxide in a sample and can be used to distinguish N-oxides from hydroxylated metabolites (Ramanathan et al. Anal. Chem. 2000; 72: 1352). To demonstrate the practical application of thermal fragmentation of N-oxides, liquid chromatography (LC)/APCI-MS was used to distinguish an N-oxide drug from its hydroxylated metabolite in an unprocessed rat urine sample, despite the fact that the drug and its metabolite were not fully resolved by HPLC.
authors.affiliation: Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: W
authors.initials: W
authors.lastname: Tong
authors.forename: S K
authors.initials: SK
authors.lastname: Chowdhury
authors.forename: J C
authors.initials: JC
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Zhong
authors.forename: K B
authors.initials: KB
authors.lastname: Alton
authors.forename: J E
authors.initials: JE
authors.lastname: Patrick
mesh_terms: D000818:Animals; D001274:Atmospheric Pressure; D002853:Chromatography, Liquid; D003497:Cyclic N-Oxides / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000652:urine; D006900:Hydroxylation; D004364:Pharmaceutical Preparations / Q000378:metabolism; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D013696:Temperature; D014556:Urine / Q000737:chemistry
chemical_list: D003497:Cyclic N-Oxides; D004364:Pharmaceutical Preparations