Protocol - Biomarker of exposure to nicotine-containing products - Saliva
This is the laboratory protocol for measuring salivary cotinine. It is used to screen for smoking status and to estimate exposure to secondhand smoke (SHS).
A biospecimen is collected from the respondent to measure cotinine, a marker of either smoking or environmental tobacco smoke exposure. One of the most common methods of collection is via a urine sample obtained from the respondent.
The gold standard to measure cotinine levels is blood. Collection of saliva is less invasive and saliva and blood levels of cotinine are highly correlated. Choosing saliva over serum or plasma is based on convenience for investigator, no need for phlebotomist, no pain for subjects, and can be collected at home and mailed to the researcher.
The TRRP recommends oral suctioning infants and toddlers for saliva if a sample is needed for cotinine measurement. The TRRP also recommends continuing collection until at least 2-3 ml of saliva (excluding foam) have been collected, marking the tubes with a line to which the saliva should be collected.
Collect saliva by having subjects expectorate into a vial while stimulating saliva flow with one of the three methods employed in previous studies: (a) sucking on a lemon candy, (b) dissolving a sugar cube in the mouth, or (c) chewing on parafilm. Approximately 2-3 minutes is required to collect each saliva sample.
Concentrations of cotinine determined by capillary gas
chromatography with nitrogen ± phosphorus detection, 11 using 1-methyl-5-(2-pyridyl)-pyrrolidin- 2-one (ª ortho-cotinineº) as the internal standard.
Personnel and Training Required
Training on saliva collection and shipping techniques.
Saliva collection and shipping kits.
|Specialized requirements for biospecimen collection||No|
|Average time of greater than 15 minutes in an unaffected individual||No|
Mode of Administration
Child, Adolescent, Adult, Senior, Pregnancy
All participants who can provide a saliva sample.
Saliva is easy to obtain through a non-invasive method and was chosen for this reason. Collection of saliva is less invasive and saliva and blood levels of cotinine are highly correlated. Choosing saliva over serum or plasma is based on convenience for investigator, no need for phlebotomist, no pain for subjects, and can be collected at home and mailed to the researcher.
|caDSR Common Data Elements (CDE)||Saliva Cotinine Assay Concentration Level Code||6454563||CDE Browser|
Process and Review
Protocol Name from Source
Saliva cotinine levels as a function of collection method
Schneider NG, Jacob P, Nilsson F, Leischow S, Benowitz N, and Olmstead R. Saliva cotinine levels as a function of collection method. Addiction (1997): 92(3): 347-351.
Rose J, Levin E, and Benowitz N. Saliva Nicotine as an Index of Plasma Levels in Nicotine Skin Patch Users. Therapeutic Drug monitoring. 1993; 15: 431-435.
Avila-Tang E, Al-Delaimy WK, Ashley DL, Benowitz N, Bernert JT, Kim S, Samet JM, Hecht SS. (2013). Assessing secondhand smoke using biological markers. Tob Control, 22(3): 164-871.
Breimer DD, Danhof M. Saliva: a fluid for measuring drug concentrations. Pharm Int 1980: 1:9-11.
Jacob P, Wilson M, Benowitz, N. Improved gas chromatographic method for the determination of nicotine and cotinine in biologic fluids. J Chromatogr 1981: 222: 61-70.
Jacob P, Yu, L., Duan, M., Ramos, LI., Yturralde, O., and Benowitz, N.L. (2011). Determination of the nicotine metabolites cotinine and trans-3’-hydroxycotinine in biologic fluids of smokers and non-smokers using liquid chromatography-tandem mass spectrometry: Biomarkers for tobacco smoke exposure and for phenotyping cytochrome P460 2A6 activity. Journal of Chromatography B, 879: 267-276.
Pirkle, J. L., Flegal, K. M., Bernert, J. T., Brody, D. J., Etzel, R. A., & Maurer, K. R. (1996). Exposure of the US population to environmental tobacco smoke. The Third National Health and Nutrition Examination Survey, 1988 to 1991. JAMA, 275, 1233-124
Rose JE, Herskovice JE, Trilling Y, Jarvik ME. Transdermal nicotine reduces cigarette craving and nicotine preference. Clin Pharmacol Ther 1985; 38: 450-6.
St. Helen, G., Novalen, M., Heitjan, D.F. (2012). Reproducibility of the Nicotine Metabolite Ratio in Cigarette Smokers. Cancer Epidemiology, Biomarkers & Prevention, 21(7) 1105-1114.
|Variable Name||Variable ID||Variable Description||dbGaP Mapping|
|PX091702000000||Protocol 091702 - proprietary. Check DCW for more||N/A|
Biomarker of exposure to nicotine-containing products
November 28, 2017
Cotinine is a major metabolite of nicotine and is an indicator of exposure to nicotine from tobacco or other nicotine containing products.
To assess smoking and environmental tobacco smoke (ETS) exposure by measuring cotinine, a metabolite of nicotine. To screen for tobacco use and quantity and to estimate exposure to secondhand smoke (SHS) and all tobacco exposure. Also used as an outcome measure in smoking cessation trials to determine if an individual has quit smoking.
cotinine, Centers for Disease Control and Prevention, CDC, National Health and Nutrition Examination Survey, NHANES, Respiratory