Reproducibility of the nicotine metabolite ratio in cigarette smokers

Gideon St.Helen, Maria Novalen, Daniel F. Heitjan, Delia Dempsey, Peyton Jacob, Adel Aziziyeh, Victoria C. Wing, Tony P. George, Rachel F. Tyndale, Neal L. Benowitz

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


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. Conclusion: 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. Impact: One measurement may reliably estimate a smoker's NMR for use as an estimate of the rate of nicotine metabolism.

Original languageEnglish (US)
Pages (from-to)1105-1114
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Issue number7
StatePublished - Jul 2012

ASJC Scopus subject areas

  • Epidemiology
  • Oncology


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