RESUMEN
The potential endogenous nitrosation of nicotine and/or nicotine metabolites has led to speculation on the possible formation of 4-(methylnitrosamino)-4-(3-pyridyl)butyric acid (iso-NNAC) in smokers. A gas chromatographic method with thermal energy analytical detection is described for the determination of iso-NNAC in tobacco, tobacco smoke and urine. Sample pre-concentration is performed using C18 extraction cartridges prior to esterification of iso-NNAC using ethereal diazomethane solution. Sample clean-up includes chromatography on aluminum and silica, and fractionation using high-performance liquid chromatography. The detection limits for iso-NNAC in tobacco, tobacco smoke and urine are 2 ng/g tobacco, 0.1 ng/cigarette and 20 ng/l urine, respectively.
Asunto(s)
Carcinógenos/análisis , Cromatografía de Gases/métodos , Nicotiana/química , Nitrosaminas/análisis , Plantas Tóxicas , Humo/análisis , Fumar/orina , Animales , Humanos , Concentración de Iones de Hidrógeno , Ratas , Valores de ReferenciaRESUMEN
The potential endogenous nitrosation of nicotine and cotinine to yield 4-(N-methylnitrosamino)-4-(3-pyridyl)butyric acid (Iso-NNAC) has been studied in smokers and non-smokers. Following i.v. administration of 100 micrograms Iso-NNAC to rats, excretion in urine (67.4 +/- 25.4%) and feces (6.1 +/- 1.6%) occurred within 24 h. The urinary excretion of nitrate, nicotine, cotinine and Iso-NNAC were determined in 24 h urine samples from 19 smokers and 10 non-smokers. Iso-NNAC excretion was found on four occasions (44, 65, 74 and 163 ng/day) in smokers; non-smokers did not excrete Iso-NNAC. Oral administration of nicotine (n = 8; 12-40 mg) and cotinine (n = 3; 40-60 mg) to abstinent smokers did not result in Iso-NNAC excretion, even after oral nitrate (150 mg) supplementation. However, Iso-NNAC was found in cigarette tobacco (10-330 ng/g) and mainstream cigarette smoke (1.1-5.5 ng/cig.). Our studies suggest that the occasional presence of Iso-NNAC in smokers' urine results from exogenous exposure to the preformed compound in mainstream cigarette smoke and not from endogenous nitrosation of nicotine and its metabolites.
Asunto(s)
Cotinina/metabolismo , Nicotina/metabolismo , Nitrosaminas/orina , Administración Oral , Adulto , Animales , Cromatografía de Gases , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ratas , Ratas Sprague-Dawley , Fumar/orinaRESUMEN
The main metabolite of the herbicide pyridate is 3-phenyl-4-hydroxy-6-chlorpyridazine (CL9673). A high-performance liquid chromatographic method with amperometric detection is described for determining CL9673 at residue levels in water samples. Sample preconcentration is performed by passage through a C18 extraction cartridge. A recovery study using tap water samples spiked with CL9673 at a concentration of 0.1 micrograms/l showed a recovery of 84.8% (coefficient of variation 6.2%). The method is suitable for the determination of CL9673 in drinking and groundwater.