title: Oral fluid nicotine markers to assess smoking status and recency of use.
abstract: BACKGROUND
  Oral fluid collection is noninvasive and easily observed making it an attractive matrix for objectively determining smoking status. Despite large intersubject variability, cotinine oral fluid concentrations correlate with cigarettes smoked per day (CPD). Few studies, however, assessed nicotine markers in oral fluid other than cotinine; other markers might improve smoking status assessment and/or time of last cigarette.
  
  
  METHODS
  Smoking histories and oral fluid specimens were collected from nontreatment-seeking light (1-10 CPD) and heavy smokers (greater than 10 CPD) and from environmentally exposed and nonexposed nonsmokers who provided written informed consent for this Institutional Review Board-approved study. Nicotine, cotinine, hydroxycotinine (OH-cotinine), and norcotinine oral fluid concentrations were quantified by liquid chromatography tandem mass spectrometry.
  
  
  RESULTS
  Comparison of 1, 3, and 10 ng/mL oral fluid liquid chromatography tandem mass spectrometry cutoffs demonstrated that 10-ng/mL cutoffs performed optimally for cotinine, OH-cotinine, nicotine, and norcotinine identifying 98%, 97%, 88%, and 15% of self-reported smokers; 1% nonsmokers had greater than 10 ng/mL cotinine. No self-reported nonsmoker had greater than 10 ng/mL OH-cotinine, nicotine, or norcotinine. Norcotinine was only identified in smokers' oral fluid. Oral fluid nicotine, cotinine, and nicotine/cotinine ratios were correlated with time of last smoking (r = -0.53, -0.23, and -0.51; P < 0.05) and CPD (r = 0.35, 0.26, and 0.33; P < 0.01), respectively.
  
  
  CONCLUSIONS
  OH-cotinine performed slightly better than cotinine for distinguishing smokers from nonsmokers and should be considered as an additional oral fluid smoking indicator. Further research is required to determine if oral fluid norcotinine is a marker for distinguishing light and heavy smokers. Moderate correlations suggest nicotine, cotinine, and nicotine/cotinine ratios may be useful for determining smoking recency in "spot samples" collected during nicotine cessation treatment.
authors.affiliation: Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
authors.forename: Karl B
authors.initials: KB
authors.lastname: Scheidweiler
authors.forename: Gina F
authors.initials: GF
authors.lastname: Marrone
authors.forename: Diaa M
authors.initials: DM
authors.lastname: Shakleya
authors.forename: Edward G
authors.initials: EG
authors.lastname: Singleton
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Heishman
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D003367:Cotinine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000032:analysis* / Q000378:metabolism*; D012463:Saliva / Q000737:chemistry*; D012907:Smoking; D055815:Young Adult
chemical_list: D015415:Biomarkers; C001381:hydroxycotinine; D009538:Nicotine; D003367:Cotinine