Urine nicotine metabolite concentrations in relation to plasma cotinine during low-level nicotine exposure

Nicotine Tob Res. 2009 Aug;11(8):954-60. doi: 10.1093/ntr/ntp092. Epub 2009 Jun 12.


Introduction: Plasma or saliva cotinine concentrations are used widely as biomarkers of secondhand smoke (SHS) exposure and have been associated with the risk of SHS-related disease. Concentrations of cotinine and other nicotine metabolites are considerably higher in urine than in plasma or saliva, making chemical analysis easier. In addition, urine is often more convenient to collect in some SHS exposure studies. The optimal use of nicotine metabolites in urine, singly or in combination, with or without correction for urine creatinine concentration, to estimate plasma cotinine concentration with low-level nicotine exposure has not been determined.

Methods: We dosed 36 nonsmokers with 100, 200, or 400 microg deuterium-labeled nicotine (simulating exposure to SHS) by mouth daily for 5 days and then measured plasma and urine cotinine and metabolites at various intervals over 24 hr.

Results: A plasma cotinine concentration of 1 ng/ml corresponds on average to a daily intake of 100 microg nicotine. Cotinine concentrations in urine averaged four to five times those in plasma. Correction of urine cotinine for creatinine concentration improved the correlation between urine and plasma cotinine. Measuring multiple cotinine metabolites in urine did not improve the correlation with plasma cotinine, compared with the use of urine cotinine alone.

Discussion: Measurement of urine cotinine corrected for creatinine concentration appears to be the best predictor of plasma cotinine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cotinine / blood*
  • Dose-Response Relationship, Drug
  • Humans
  • Nicotine / administration & dosage
  • Nicotine / blood*
  • Nicotine / urine*


  • Nicotine
  • Cotinine