title: Matrix-bound 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in tobacco: quantification and evidence for an origin from lignin-incorporated alkaloids.
abstract: Substantial quantities of the carcinogenic tobacco-specific N-nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (1; NNK) are still found in the mainstream smoke of tobacco exhaustively extracted with water, indicating the presence of an insoluble, matrix-bound form. Soluble and matrix-bound concentrations of 1 in tobacco were determined by applying a new method using sequential aqueous extraction at room temperature and at 130 °C. On average, 77% and 53% of the total content of 1 were matrix-bound in air-cured (Burley type) and flue-cured tobaccos, respectively. Thermal release of 1 from its matrix-bound form above ca. 200 °C can account for a large fraction of its concentration in cigarette mainstream smoke. An already matrix-bound alkaloid precursor of matrix-bound 1 was identified in vascular tissue of green leaf midribs. The incubation of vascular cell-wall preparations with the lignin precursor coniferyl alcohol and isotopically labeled nicotine or pseudooxynicotine (2) led to the formation of labeled matrix-bound 1 after nitrosation, suggesting that incorporation of nicotine or its oxidized product 2 during lignin polymerization is the origin of the formation of matrix-bound 1.
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A. , Quai Jeanrenaud 5, CH-2000 Neuchâtel, Switzerland.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Lang
authors.forename: Aline
authors.initials: A
authors.lastname: Vuarnoz
mesh_terms: D000470:Alkaloids / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification*; D002074:Butanones / Q000032:analysis / Q000737:chemistry; D008031:Lignin / Q000032:analysis* / Q000737:chemistry / Q000302:isolation & purification; D015394:Molecular Structure; D009538:Nicotine / Q000031:analogs & derivatives / Q000032:analysis* / Q000737:chemistry; D009602:Nitrosamines / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification; D018515:Plant Leaves / Q000737:chemistry; D012906:Smoke; D014026:Nicotiana / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D002074:Butanones; D009602:Nitrosamines; D012906:Smoke; C081694:pseudooxynicotine; D009538:Nicotine; C005222:methylethyl ketone; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D008031:Lignin