title: Reproducibility of the nicotine metabolite ratio in cigarette smokers.
abstract: BACKGROUND
  The nicotine metabolite ratio (NMR or 3-hydroxycotinine/cotinine) has been used to phenotype CYP2A6-mediated nicotine metabolism. Our objectives were to analyze (i) the stability of NMR in plasma, saliva, and blood in various storage conditions, (ii) the relationship between NMRs derived from blood, plasma, saliva, and urine, and (iii) the reproducibility of plasma NMR in ad libitum cigarette smokers.
  
  
  METHODS
  We analyzed data from four clinical studies. In studies 1 and 2, we assessed NMR stability in saliva and plasma samples at room temperature (~22°C) over 14 days and in blood at 4°C for up to 72 hours. In studies 2 and 3, we used Bland-Altman analysis to assess agreement between blood, plasma, saliva, and urine NMRs. In study 4, plasma NMR was measured on six occasions over 44 weeks in 43 ad libitum smokers.
  
  
  RESULTS
  Reliability coefficients for stability tests of NMR in plasma and saliva at room temperature were 0.97 and 0.98, respectively, and 0.92 for blood at 4°C. Blood NMR agreed consistently with saliva and plasma NMRs but showed more variability in relation to urine NMR. The reliability coefficient for repeated plasma NMR measurements in smokers was 0.85.
  
  
  CONCLUSIONS
  The NMR is stable in blood, plasma, and saliva at the conditions tested. Blood, plasma, and saliva NMRs are similar whereas urine NMR is a good proxy for these NMR measures. Plasma NMR was reproducible over time in smokers.
  
  
  CONCLUSIONS
  One measurement may reliably estimate a smoker's NMR for use as an estimate of the rate of nicotine metabolism.
authors.affiliation: Center for Tobacco Control Research and Education, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Gideon
authors.initials: G
authors.lastname: St Helen
authors.forename: Maria
authors.initials: M
authors.lastname: Novalen
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Heitjan
authors.forename: Delia
authors.initials: D
authors.lastname: Dempsey
authors.forename: Peyton
authors.initials: P
authors.lastname: Jacob
authors.forename: Adel
authors.initials: A
authors.lastname: Aziziyeh
authors.forename: Victoria C
authors.initials: VC
authors.lastname: Wing
authors.forename: Tony P
authors.initials: TP
authors.lastname: George
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
mesh_terms: D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis*; D065637:Cytochrome P-450 CYP2A6; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000378:metabolism*; D010641:Phenotype; D011379:Prognosis; D015203:Reproducibility of Results; D012463:Saliva / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009538:Nicotine; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6