Mass spectrometric analysis of tobacco-specific hemoglobin adducts

Abstract

Hemoglobin adducts of the common metabolite of the tobacco-specific nitrosamine (TSNA) 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) and of 4-aminobiphenyl (4-ABP) were quantified in blood samples from smokers and nonsmokers to test their suitability for biomonitoring tobacco smoke exposure. Additionally, TSNA adducts were measured in nasal snuff users. Mild alkaline treatment of hemoglobin releases 4-ABP and HPB, which were analyzed in parallel by capillary gas chromatography with electronic impact or negative ion chemical-ionization mass spectrometry (EI- or NICI-GC-MS). Samples of snuff users showed high levels of HPB adducts not correlated with the amount or type of snuff used. HPB concentrations in smokers and nonsmokers, however, were much lower, with no group-specific differences detectable. In contrast, 4-ABP adduct levels were much higher in smokers than in nonsmokers, confirming the significant difference between these two groups reported by others.

Toenail Nicotine Level as a Novel Biomarker for Lung Cancer Risk

“…However, most available tobacco biomarkers, such as urine and salivary cotinine (7)(8)(9), are short-lived. One of the longer-term biomarkers for tobacco exposure is 4-aminobiphenyl adducts to hemoglobin (10,11), but it has limited value in epidemiologic studies because of lack of specificity, cost, and poor prediction of lung cancer risk (12,13). Other tobacco-specific nitrosamines such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol have recently been used to determine lung cancer risk for heavy smokers (13,14), but they are prone to significant metabolic variability because of age and other factors, a nonlinear association with exposure, and the need for sophisticated laboratory analyses and caution in handling these carcinogenic chemicals (15,16).…”