MetabolicN-oxidation of 3-substituted pyridines: Identification of products by mass spectrometry

Abstract

The mass spectral characteristics of the N-oxides of a range of 3-substituted pyridines, and of quinoline and isoquinoline, are described. The molecular ion is the base peak in the majority of cases, provided that thermolysis is minimized when using the direct probe or gas chromatography inlets. Chromatographic and mass spectral evidence is presented which indicates that biological oxidation of the heteroaromatic nitrogen of 3-substituted pyridines is a route of metabolism in vivo and in vitro.

Safety and efficacy of pyridine and pyrrole derivatives belonging to chemical group 28 when used as flavourings for all animal species

“…3-Ethylpyridine was converted to the corresponding N-oxide by fortified hepatic microsomal preparations from hamster, guinea-pig, rabbit, rat and mouse, and by pulmonary microsomal preparations from guinea-pig and rabbit (Cowan et al, 1978 as quoted by EFSA CEF Panel 2013). In vivo, no urinary N-oxidation products were found for dimethylpyridines, the major metabolism being the result of the oxidation of one of the methyl groups.…”

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to Flavouring Group Evaluation 24 (FGE.24): Pyridine, pyrrole, indole and quinoline derivatives from chemical group 28 (Commis

“…3-Methylpyridine was converted to the corresponding N-oxide by fortified hepatic microsomal preparations from hamster, guinea-pig, rabbit, rat and mouse, and by pulmonary microsomal preparations from guinea-pig and rabbit (Cowan et al, 1978).…”

“…The metabolites isolated from urine were 1-(3-pyridyl)ethanol, N-methylated 1-(3-pyridyl)ethanol and (3-pyridyl)-1,2-ethanediol which was oxidised to nicotinic acid (McKee et al, 1987) (Figure III.4). 3-Acetylpyridine was converted to the corresponding N-oxide by fortified hepatic microsomal preparations from hamster, guinea-pig, rabbit, rat and mouse, and by pulmonary microsomal preparations from guinea-pig and rabbit (Cowan et al, 1978). Similar in vitro results were obtained when 3-acetylpyridine was incubated with hepatic supernatant fraction and microsomal fractions from rats, guinea pigs, rabbits, hamster and mice, where they identified N-oxide metabolites of both 1-(3-pyridyl)ethanol and 3-acetylpyridine itself.…”

“…In contrast to 3-acetylpyridine, no N-oxidation products of 3-hydroxypyridine were found after incubation with liver microsomes from hamster, guinea-pig, rabbit, rat and mouse. (Cowan et al, 1978). (McKennis et al, 1964) and with microsomal preparation from liver of rats, guinea-pigs, rabbits, hamster and mice (in frame) .…”

“…No N-oxidation products of nicotinic acid were found after incubation with liver microsomes from hamster, guinea-pig, rabbit, rat and mouse (Cowan et al, 1978). Nicotinic acid is a vitamine metabolite of the nicotinates (Lehninger, 1982).…”