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

Psychopharmacology (Berl). 2006 Dec;189(3):345-54. doi: 10.1007/s00213-006-0586-x. Epub 2006 Oct 7.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cotinine / analogs & derivatives*
  • Cotinine / analysis
  • Cotinine / urine*
  • Female
  • Filtration
  • Humans
  • Middle Aged
  • Nicotine / administration & dosage*
  • Nicotinic Agonists / administration & dosage*
  • Saliva / chemistry*
  • Saliva / metabolism
  • Smoking / metabolism*
  • Smoking / urine
  • Tars / analysis*


  • Nicotinic Agonists
  • Tars
  • hydroxycotinine
  • Nicotine
  • Cotinine