Research Article

Estimation of cotinine level among the tobacco users and nonusers: A cross-sectional study among the Indian population

Sukhvinder Singh Oberoi* and Avneet Oberoi

Published: 02/15/2021 | Volume 5 - Issue 1 | Pages: 003-008


Background: Epidemiological studies in smokers indicate a dose-response relationship between the number of cigarettes smoked per day and the risk of developing certain smoking related diseases. The alkaloid nicotine is the major pharmacologically active substance in tobacco.

Objective: To estimate the cotinine level excretion in urine among smoked and smokeless tobacco users and nonsmokers among the Indian population.

Materials and method: The study sample consisted of 250 subjects who were apparently healthy, asymptomatic and not using any drug. The study sample was divided into smoked tobacco users (bidi and cigarette), smokeless tobacco users, both smoked and smokeless tobacco users and controls (non-users of tobacco in the past or present).

Results: The mean Cotinine level in urine was significantly (p – value < 0.05) more among smoked tobacco users in comparison to smokeless tobacco users and non-users of tobacco. Whereas, the mean Cotinine level in urine was significantly (p - value < 0.05) more among smokeless tobacco users in comparison to non-users of tobacco.

Conclusion: The mean cotinine levels among smokers and both smokeless and smoked tobacco users were found to be higher than only smokeless tobacco users and non-users of tobacco.

Read Full Article HTML DOI: 10.29328/journal.jatr.1001014 Cite this Article


  1. Benowitz NL. Clinical pharmacology of nicotine: implications for understanding, preventing, and treating tobacco addiction. Clin Pharmacol Ther. 2008; 83: 531–541. PubMed:
  2. Hecht SS, Carmella SG, Murphy SE, Riley WT, Le C, et al. Similar exposure to a tobacco-specific carcinogen in smokeless tobacco users and cigarette smokers. Cancer Epidemiol Biomarkers Prev. 2007; 16: 1567–1572. PubMed:
  3. P.H.S. Department of Health and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Washington DC: US Government Printing Office. 2006. PubMed:
  4. DHHS (CDC) Publication No. 87-8398, IARC. Monograph on the Evaluation of Carcinogenic Risks to Humans. Lyon, France: WHO. 2004.
  5. Benowitz NL. Pharmacologic aspects of cigarette smoking and nicotine addiction. N Engl J Med. 1988; 319: 1318–1330.
  6. Wynder EL, Hoffmann D. Tobacco and Tobacco Smoke. Studies in Experimental Carcinogenesis. New York: Academic Press. 1967.
  7. Hoffmann D, Djordjevic MV, Hoffmann I. The changing cigarette. Prev Med. 1997; 26: 427–434. PubMed:
  8. Wynder EL, Hoffmann D. Tobacco and health: A societal challenge. N Engl J Med. 1979; 300: 894–903. PubMed:
  9. Benowitz NL. Pharmacologic aspects of cigarette smoking and nicotine addiction. N Engl J Med. 1988; 319: 1318–1330.         PubMed:
  10. Benowitz NL. Cotinine as a Biomarker of Environmental Tobacco Smoke Exposure. Epidemiol Rev0 1996; 18: 188-204. PubMed:
  11. Benowitz NL. The human pharmacology of nicotine. Res Adv Alcohol Drug Probl. 1986; 9: 1–52.
  12. Hurt RD Robertson CR. Prying open the door to the tobacco industry’s secrets about nicotine. The Minnesota tobacco trial. JAMA. 1998; 280: 1173–1181. PubMed:
  13. Hukkanen J, Jacob P, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev. 2005; 57: 79-115. PubMed:
  14. Matt GE, Quintana PJ, Liles S et al. Evaluation of urinary trans-3’-hydroxycotinine as a biomarker of children’s environmental tobacco smoke exposure. Biomarkers. 2006; 11: 507-523. PubMed:
  15. Benowitz NL, Jacob P III, Ahijevych K, Jarvis MJ, Hall S, et al. Biochemical verification of tobacco use and cessation. Nicotine Tob Res 2002; 4: 149–159. PubMed:
  16. Jacob P III, Hatsukami DK, Severson H, Hall S, Yu L, et al. Anabasine and anatabine as biomarkers for tobacco use during nicotine replacement therapy. Cancer Epidemiol Biomarkers Prev. 2002; 11: 1668–1673. PubMed:
  17. Hecht SS. Human urinary carcinogen metabolites: biomarkers for investigating tobacco and cancer. Carcinogenesis. 2002; 23: 907–922. PubMed:
  18. Bernert JT, Jacob P 3rd, Holiday DB, Benowitz NL, Sosnoff CS, et al. Interlaboratory comparability of serum cotinine measurements at smoker and nonsmoker concentration levels: a round -robin study. Nicotine Tob Res. 2009; 11: 1458–1466.
  19. Jacob P III, Byrd GD. Use of gas chromatographic and mass spectrometric techniques for the determination of nicotine and its metabolites. In: Gorrod JW, Jacob P III. Analytical Determination of Nicotine and Related Compounds and Their Metabolites. Elsevier; Amsterdam. 1999; 191-224.
  20. Al-Delaimy WK. Hair as a biomarker for exposure to tobacco smoke. Tob Control. 2002; 11: 176–182. PubMed:
  21. Al-Delaimy WK, Mahoney GN, Speizer FE, Willett WC. Toenail nicotine levels as a biomarker of tobacco smoke exposure. Cancer Epidemiol Biomarkers Prev. 2002; 11: 1400–1404. PubMed:
  22. Ryu HJ, Seong MW, Nam MH, Kong SY, Lee DH. Simultaneous and sensitive measurement of nicotine and cotinine in small amounts of human hair using liquid chromatography/ tandem mass spectrometry. Rapid Commun Mass Spectrom. 2006; 20: 2781–2782. PubMed:
  23. Stepanov I, Hecht SS, Lindgren B, Jacob P 3rd, Wilson M, et al. Relationship of human to enail nicotine, cotinine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol to levels of these biomarkers in plasma and urine. Cancer Epidemiol Biomarkers Prev. 2007; 16: 1382–1386. PubMed:
  24. Jarvis MJ, Primatesta P, Erens B, Feyerabend C, Bryant A. Measuring nicotine intake in population surveys: comparability of saliva cotinine and plasma cotinine estimates. Nicotine Tob Res. 2003; 5: 349–355. PubMed:
  25. Bernert JT Jr. McGuffey JE, Morrison MA, Pirkle JL. Comparison of serum and salivary cotinine measurements by a sensitive high -performance liquid chromatography-tandem mass spectrometry method as an indicator of exposure to tobacco smoke among smokers and nonsmokers. J Anal Toxicol. 2000; 24: 333–339.
  26. Jarvis MJ, Tunstall-Pedoe H, Feyerabend C, Vesey C, Saloojee Y. Comparison of tests used to distinguish smokers from nonsmokers. Am J Public Health 1987; 77: 1435–1148. PubMed:
  27. Davis RA, Curvall M. Determination of nicotine and its metabolites in biological fluids in vivo studies. In: Gorrod JW, Jacob P III, eds. Analytical Determination of Nicotine and Related Compounds and Their Metabolites. Amsterdam: Elsevier. 1999; 583–644.
  28. Byrd GD, Chang KM, Greene JM, deBethizy JD. Evidence for urinary excretion of glucuronide conjugates of nicotine, cotinine, and trans-3’ – hydroxycotinine in smokers. Drug Metab Dispos. 1992; 20: 192-197. PubMed:
  29. Lequant NT, Roussel G, Roche D, Migueres ML, Chretien J, Ekindjian OG. Urine collection for nicotine and cotinine measurement in study on nicotine addicts. Pathol Biol (Paris). 1994; 42: 191-196. PubMed:
  30. Trout D, Decker J, Mueller C, Bernert JT, Pirkle J. Exposure of casino employees to environmental tobacco smoke. J Occup Environ Med. 1998; 40: 270-276. PubMed:
  31. Apseloff G, Ashton HM, Friedman H, Gerber N. The importance of measuring cotinine levels to identify smokers in clinical trials. Clin Pharmacol Ther. 1994; 56: 460-462. PubMed:
  32. Barrueco M, Cordovilla R, Hernandez-Mezquita MA, Gonzalez JM, de Castro J, et al. The truthfulness of the answers of children, adolescents and young people to surveys on tobacco consumption conducted in schools. Med Clin (Barc). 1999; 112: 251-254. PubMed:
  33. Scherer G, Richter E. Biomonitoring exposure to environmental tobacco smoke (ETS): a critical reappraisal. Hum Exp Toxicol. 1997; 16: 449-459. PubMed:
  34. Carey IM, Cook DG, Strachan DP. The effects of environmental tobacco smoke exposure on lung function in a longitudinal study of British adults. Epidemiology. 1999; 10: 319-326.  PubMed:
  35. de Waard F, Kemmeren JM, van Ginkel LA, Stolker AA. Urinary cotinine and lung cancer risk in a female cohort. Br J Cancer. 1995; 72: 784-787. PubMed:
  36. Lawson GM, Hurt RD, Dale LC, Offord KP, Croghan IT, et al. Application of urine cotinine and plasma cotinine concentrations to assessment of nicotine replacement in light, moderate, and heavy smokers undergoing transdermal therapy. J Clin Pharmacol. 1998; 38: 510-516. PubMed:
  37. Benowitz NL, Jacob P III. Metabolism of nicotine to cotinine studied by a dual stable isotope method. Clin Pharmacol Ther. 1994; 56: 483–493. PubMed:
  38. Avila-Tang E, Al-Delaimy WK, Ashley DL, Benowitz N, Bernert JT, Kim S, et al. Assessing secondhand smoke using biological markers. Tob Control. 2013; 22: 164-171. PubMed:  
  39. Benowitz NL, Jacob P 3rd. Daily intake of nicotine during cigarette smoking. Clin Pharmacol Ther 1984; 35: 499-504. PubMed:
  40. Behera D, Uppal R, Majumdar S. Urinary levels of nicotine & cotinine in tobacco users. Indian J Med Res. 2003; 118: 129-133. PubMed:
  41. Macaron C, Macaron Z, Maalouf MT, Macaron N, Moore A. Urinary cotinine in narguila or chicha tobacco smokers. J Med Liban. 1997; 45: 19-20. PubMed:
  42. Chen J, Kettermann A, Rostron BL, Day HR. Biomarkers of exposure among U.S. cigar smokers: an analysis of 1999-2012 National Health and Nutrition Examination Survey (NHANES) data. Cancer Epidemiol Biomarkers Prev. 2014; 23: 2906-2915. PubMed:
  43. Blackford AL, Yang G, Hernandez-Avila M, Przewozniak K, Zatonski W, et al. Cotinine concentration in smokers from different countries: relationship with amount smoked and cigarette type. Cancer Epidemiol Biomarkers Prev. 2006; 15: 1799-1804. PubMed:
  44. Centers for Disease Control and Prevention (CDC). National Report on Human Exposure to Environmental Chemicals. Results. NHANES IV. CDC CAS no.486-56-6. 3-21-2002.
  45. Jarvis MJ, Boreham R, Primatesta P, Feyerabend C, Bryant A. Nicotine yield from machine-smoked cigarettes and nicotine intakes in smokers: evidence from a representative population survey. J Natl Cancer Inst. 2001; 93: 134-138. PubMed:
  46. Weiss ST, Tager IB, Schenker M, Speizer FE. The health effects of involuntary smoking. Am Rev Respir Dis. 1983; 128: 933-942. PubMed:
  47. Benowitz NL, Bernert JT, Caraballo RS, Holiday DB, Wang J. Optimal Serum Cotinine Levels for Distinguishing Cigarette Smokers and Nonsmokers Within Different Racial/Ethnic Groups in the United States between 1999 and 2004. Am J Epidemiol. 2009; 169: 236-248. PubMed:
  48. Zielinska-Danch W, Wardas W, Sobczak A, et al. Estimation of urinary cotinine cut-off points distinguishing nonsmokers, passive and active smokers. Biomarkers 2007; 12: 484-496. PubMed:
  49. Idle JR. Titrating exposure to tobacco smoke using cotinine—a minefield of misunderstandings. J Clin Epidemiol. 1990; 43: 313–317. PubMed:
  50. Jacob P 3rd, Yu L, Shulgin AT, Benowitz NL. Minor tobacco alkaloids as biomarkers for tobacco use: Comparison of cigarette, smokeless tobacco, cigar and pipe users. Am J Public Health. 1999; 89: 731-736. PubMed: