title: Thermally induced N-to-O rearrangement of tert-N-oxides in atmospheric pressure chemical ionization and atmospheric pressure photoionization mass spectrometry: differentiation of N-oxidation from hydroxylation and potential determination of N-oxidation site.
abstract: N-Oxides are known to undergo deoxygenation during atmospheric pressure chemical ionization (Ramanathan, R.; Su, A.-D.; Alvarez, N.; Blumenkrantz, N.; Chowdhury, S. K.; Alton, K.; Patrick, J. Anal. Chem. 2000, 72, 1352-1359) resulting from thermal energy activation at the vaporizer of the APCI source. In addition to deoxygenation, tert-N-oxides containing an alkyl or benzyl group on the N-oxide nitrogen also undergo an N-R to O-R rearrangement (Meisenheimer arrangement, where R = alkyl or benzyl), followed by elimination of an aldehyde (or a ketone) through an internal hydrogen transfer. This has been observed under both atmospheric pressure chemical ionization and atmospheric pressure photoionization conditions. These fragment ions were not observed in the product ion spectra from the protonated molecules of the corresponding N-oxides. The elimination of an aldehyde or a ketone, thus, results from thermal energy activation at the vaporizer and is not induced by collisional activation. These fragmentations not only distinguish N-oxides from isomeric hydroxylated metabolites but also provide a potential way to determine the position of N-oxidation when a metabolite (or molecule) contains multiple N-oxidation sites that are in different chemical environments.
authors.affiliation: Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Ma
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Chowdhury
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Alton
mesh_terms: D001274:Atmospheric Pressure; D001286:Atropine Derivatives / Q000737:chemistry; D003024:Clozapine / Q000031:analogs & derivatives / Q000737:chemistry; D003497:Cyclic N-Oxides / Q000737:chemistry*; D005021:Ethylamines / Q000737:chemistry; D006900:Hydroxylation; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010777:Photochemistry; D011725:Pyridines / Q000737:chemistry; D012680:Sensitivity and Specificity; D013696:Temperature
chemical_list: D001286:Atropine Derivatives; D003497:Cyclic N-Oxides; D005021:Ethylamines; D011725:Pyridines; C056207:triethylamine-N-oxide; C013229:pyridine N-oxide; D003024:Clozapine; C079149:clozapine N-oxide