A comparison of nicotine dose estimates in smokers between filter analysis, salivary cotinine, and urinary excretion of nicotine metabolites

Abstract

Rationale Nicotine uptake during smoking was estimated by either analyzing the metabolites of nicotine in various body fluids or by analyzing filters from smoked cigarettes. However, no comparison of the filter analysis method with body fluid analysis methods has been published. Objectives Correlate nicotine uptake estimates between filter analysis, salivary cotinine, and urinary excretion of selected nicotine metabolites to determine the suitability of these methods in estimating nicotine absorption in smokers of filtered cigarettes. Materials and methods A 5-day clinical study was conducted with 74 smokers who smoked 1-19 mg Federal Trade Commission tar cigarettes, using their own brands ad libitum. Filters were analyzed to estimate the daily mouth exposure of nicotine. Twenty-four-hour urine samples were collected and analyzed for nicotine, cotinine, and 3′-hydroxycotinine plus their glucuronide conjugates. Saliva samples were collected daily for cotinine analysis.Results Each method correlated significantly (p<0.01) with the other two. The best correlation was between the mouth exposure of nicotine, as estimated by filter analysis, and urinary nicotine plus metabolites. Multiple regression analysis implies that saliva cotinine and urinary output are dependent on nicotine mouth exposure for multiple days. Creatinine normalization of the urinary metabolites degrades the correlation with mouth exposure. Conclusions The filter analysis method was shown to correlate with more traditional methods of estimating nicotine uptake. However, because filter analysis is less complicated and intrusive, subjects can collect samples easily and unsupervised. This should enable improvements in study compliance and future study designs.

The Relationship Between Cigarette Smoking and Biomarkers of Exposure Across Two Study Centers in Europe

“…NNAL and its metabolite were analyzed using a solid phase extraction and liquid [11] and Pan et al [12] (LLOQ 5ng/ml ULOQ 1000ng/ml). Urinary nicotine and its metabolites were analyzed using a solid phase extraction and liquid chromatography with tandem mass spectrometry as described by St. Charles et al [6] (LLOQ 10ng/ml ULOQ 5000ng/ml). When described below, total nicotine metabolites represent the sum of the nicotine, cotinine and hydroxycotinine plus all of their glucuronide conjugates, allowing for the molecular mass of the analyte, expressed as a mass of the parent molecule.…”

“…In other studies with large numbers of subjects, a technique based on the analysis of smoked cigarette filters has been developed [6]. This method has the advantage of giving an estimate of mouth-level exposure for the cigarette actually smoked by each smoker without the need for the collection of any biofluid; however, it does not measure the amount of smoke drawn into the lungs or subsequently distributed throughout body tissues and so *Address correspondence to this author at the British American Tobacco, GR&D Regents Park Road, Southampton, SO15 8TL, UK; Tel: +44 (0)2380 793647; Fax: +44 (0)2380 793076; E-mail: Frazer_Lowe@bat.com interest has focused on the potential of biomarkers for this use [7].…”

Comparison of Exposure to Selected Cigarette Smoke Constituents in Adult Smokers and Nonsmokers in a European, Multicenter, Observational Study

“…The nicotine content in a 10-mm portion of the mouth end of the cigarette filter (26) and the cigarette butt length were determined from cigarette butts collected during the 24-hour urine collection period.…”

Intra- and inter-individual variability in urinary nicotine excretion and plasma cotinine in adult cigarette smokers

“…Nicotine equivalents (NE) is the molar sum of nicotine measured in 24 h urinary excretion of nicotine and its five major metabolites (cotinine and cotinine-N-glucuronide, trans-3 0 -hydroxycotinine and trans-3 0 -hydroxycotinine-O-glucuronide, and nicotine-N-glucuronide) (Benowitz et al, 1994;Roethig et al, 2005;Scherer et al, 2007). It has been reported that 24 h urinary excretion of NE accounts for an average of about 80-90% of the systemic nicotine intake from smoking or from a nicotine patch (Benowitz et al, 1994;Feng et al, 2007;St Charles et al, 2006). Nicotine equivalents has been widely used as a biomarker for exposure to tobacco and cigarette smoke (Frost-Pineda et al, 2008a, 2008bMendes et al, 2008;Roethig et al, 2005Roethig et al, , 2007Roethig et al, , 2008Roethig et al, , 2009Sarkar et al, 2008;Shepperd et al, 2009;St Charles et al, 2006;Stratton et al, 2000;Wang et al, 2011).…”