On the pharmacokinetics of tobacco-specific N-nitrosamines in Fischer rats

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Abstract
Methods were developed to determine the biological half-lives and rates of distribution and elimination of N'-nitrosonor-nicotine (NNN), N'-nitrosoanatabine (NAT), 4-(methylnitros-amuno)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitros-amino)-1-(3-pyridyl)-1-butanol (NNAL) in the F344 rat. The formation and persistence of an in vivo equilibrium between NNK and NNAL were also studied. The method consists of extraction and elution of the nitrosamines through a Clin-Elut column with ethyl acetate, followed by concentration and analysis by a gas chromatography-thermal energy analyzer. The biological half-lives for NNN and NAT were 184 and 540 min, those for NNK and NNAL ranged from 25 to 37 and 184 to 298 min, respectively. A relatively short biological half-life for the TSNA suggests a correlation with carcinogenic potency.