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A new analytical procedure has been developed for the simultaneous determination of human hemoglobin adducts from aromatic amines and tobacco-specific nitrosamines. These tobacco-related hemoglobin adducts were determined in nonsmokers, smokers, and users of nasal snuff. Adducts from aminobiphenyl compounds are good biomarkers of exposure to tobacco smoke; they are not elevated in users of nasal snuff. However, a significant contribution of environmental exposure to aromatic amines and/or the corresponding nitroaromatics makes it difficult to evaluate passive exposure to tobacco smoke. The best biomarkers for exposure to tobacco smoke should in theory be adducts arising from tobacco-specific nitrosamines. The common adduct from N'-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone releases 4-hydroxy-1-(3-pyridyl)-1-butanone from hemoglobin upon mild alkaline hydrolysis and only marginal differences are found in the adduct level in smokers and nonsmokers. The reason for this observation is not yet understood and is currently under investigation. However, the adduct formed by tobacco-specific nitrosamines is well suited for the detection of oral and nasal tobacco use. Only by simultaneous determination of both adducts formed by aromatic amines and tobacco-specific nitrosamines is it possible to differentiate between nonsmokers, smokers, and nasal snuff users.

Tobacco-specific nitrosamines are derived from nicotine and related tobacco alkaloids and can be detected in tobacco products as well as in mainstream and sidestream smoke. Two of them, N-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, are strong carcinogens in laboratory animals. Because of its organospecificity for the lung, the latter is considered to be a causative factor in tobacco-related human lung cancer. Upon metabolic activation both nitrosamines give rise to a common reactive intermediate binding to macromolecules such as DNA and haemoglobin and hydrolysing to 4-hydroxy-1-(3-pyridyl)-1-butanone. Because of easy access to large quantities of haemoglobin from blood samples, it is most suitable for biomonitoring human exposure to tobacco-specific nitrosamines. A highly sensitive analytical method for determination of femtogram amounts of 4-hydroxy-1-(3-pyridyl)-1-butanone provides an approach to assess individual exposure to active and passive smoking.