Determination of tobacco-specific N-nitrosamines in urine of smokers and non-smokers

Abstract

Tobacco-specific N-nitrosamines (TSNA) include 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N′-nitrosonornicotine (NNN), N′-nitrosoanabasine (NAB) and N′-nitrosoanatabine (NAT) and are found in tobacco and tobacco smoke. TSNA are of interest for biomonitoring of tobacco-smoke exposure as they are associated with carcinogenesis. Both NNK and NNN are classified by IARC as Group 1 carcinogens. Samples of 24 h urine collections (n = 108) were analysed from smokers and non-smokers, using a newly developed and validated LC-MS/MS method for determining total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, the major metabolite of NNK), and total NNN, NAB and NAT. TSNA levels in smokers’ urine were significantly higher than in non-smokers. In smokers, urinary excretion of total TSNA correlated significantly (r > 0.5) with markers of smoking dose, such as daily cigarette consumption, salivary cotinine and urinary nicotine equivalents and increased with the ISO tar yield of cigarettes smoked. The correlation between urinary total NNN and the smoking dose was weaker (r = 0.4–0.5). In conclusion, this new method is suitable for assessing tobacco use-related exposure to NNK, NNN, NAB and NAT.

Keywords::

• Tobacco-specific N-nitrosamines (TSNA)
• 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
• 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)
• N′-nitrosonornicotine (NNN)
• N′-nitrosoanabasine (NAB)
• N′-nitrosoanatabine (NAT)
• urine

Acknowledgments

FC, GE, JS and MM are all employees of British American Tobacco. DK and GS performed the analytical work, which was funded by British American Tobacco.

Declaration of interest: The authors report no conflict of interest.