Cited by 621Smoking Behavior and CessationSubstance Abuse Treatment and OutcomesPrenatal Substance Exposure Effects

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Biochemical Verification of Tobacco Use and Abstinence: 2019 Update

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Benowitz, Neal L, Bernert, John T, Foulds, Jonathan, Hecht, Stephen S, Jacob, Peyton, Jarvis, Martin J, Joseph, Anne, Oncken, Cheryl, Piper, Megan E·2020·Nicotine & Tobacco Research

DOI 10.1093/ntr/ntz132PMC PMC7882145

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Abstract

BACKGROUND: The changing prevalence and patterns of tobacco use, the advent of novel nicotine delivery devices, and the development of new biomarkers prompted an update of the 2002 Society for Research on Nicotine and Tobacco (SRNT) report on whether and how to apply biomarker verification for tobacco use and abstinence. METHODS: The SRNT Treatment Research Network convened a group of investigators with expertise in tobacco biomarkers to update the recommendations of the 2002 SNRT Biochemical Verification Report. RESULTS: Biochemical verification of tobacco use and abstinence increases scientific rigor and is recommended in clinical trials of smoking cessation, when feasible. Sources, appropriate biospecimens, cutpoints, time of detection windows and analytic methods for carbon monoxide, cotinine (including over the counter tests), total nicotine equivalents, minor tobacco alkaloids, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol are reviewed, as well as biochemical approaches to distinguishing cigarette smoking from use of electronic nicotine delivery devices (ENDS). CONCLUSIONS: Recommendations are provided for whether and how to use biochemical verification of tobacco use and abstinence. Guidelines are provided on which biomarkers to use, which biospecimens to use, optimal cutpoints, time windows to detection, and methodology for biochemical verifications. Use of combinations of biomarkers is recommended for assessment of ENDS use. IMPLICATIONS: Biochemical verification increases scientific rigor, but there are drawbacks that need to be assessed to determine whether the benefits of biochemical verification outweigh the costs, including the cost of the assays, the feasibility of sample collection, the ability to draw clear conclusions based on the duration of abstinence, and the variability of the assay within the study population. This paper provides updated recommendations from the 2002 SRNT report on whether and how to use biochemical markers in determining tobacco use and abstinence.

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Li, Y., Luk, T. T., Cheung, Y. T. D., Zhao, S., Zeng, Y., Tong, H. S. C., Lai, V. W. Y., & Wang, M. P. (2024) · JAMA Network Open · doi:10.1001/jamanetworkopen.2024.17796 · Cited by 13
Association between secondhand smoke exposure and rheumatoid arthritis in US never-smoking adults: a cross-sectional study from NHANES
Qi, X., Fu, J., Liu, J., Wu, X., Zheng, X., & Wang, S. (2024) · Scientific Reports · doi:10.1038/s41598-024-61950-2 · Cited by 11
The efficacy and acceptability of pharmacological monotherapies and e-cigarette on smoking cessation: a systemic review and network meta-analysis
Meng, Y., Xiang, S., Qu, L., & Li, Y. (2024) · Frontiers in Public Health · doi:10.3389/fpubh.2024.1361186 · Cited by 15
Smoking exposure and cervical cancer risk: Integrating observational and genetic evidence
Su, L., Xu, R., Ren, Y., Meng, C., Wang, P., Wu, Q., Song, L., & Du, Z. (2025) · Journal of International Medical Research · doi:10.1177/03000605251383687 · Cited by 12
“23 Based on previous studies, 24,25 we defined critical values of 0.05 and 3.00ng/mL to categorize cotinine concentrations into the following three groups: 0.05ng/mL, 0.05– 2.”
Influential
Examining the Accuracy of Self-Reported Smoking-Related Exposure among Recently Diagnosed Nonmuscle Invasive Bladder Cancer Patients
Petruzella, S., Bochner, B. H., Kenney, J. M., Whiting, K. A., Sadeghi, K. D., Benfante, N. E., Cha, E. K., Dalbagni, G. M., Donahue, T. F., Donat, S. M., et al. (2020) · The Journal of Urology · doi:10.1097/ju.0000000000001571 · Cited by 11
“0 ng/ml for no exposure.(6) To justify analyzing”
Background
A systematic review and narrative summary of couple-based smoking cessation interventions
Choi, S. H. (2022) · Journal of Social and Personal Relationships · doi:10.1177/02654075211070272 · Cited by 12
“…for Research on Nicotine and Tobacco recommends biochemical verification of tobacco use and abstinence for clinical smoking cessation interventions (Benowitz et al., 2019), yet eight studies did not validate self-reported quit rates biochemically, which can compromise the study validity (Aycock et…”
Background
Association of environmental tobacco smoke exposure with metabolic syndrome: A longitudinal Cohort Study of 71,055 never smokers
Choi, H., Lee, S. J., Kang, J., Lee, S. H., Kim, B. S., & Kim, B. J. (2022) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2022.07.009 · Cited by 11
Enhancing Tobacco Quitline Outcomes for African American Adults: An RCT of a Culturally Specific Intervention
Hooper, M. W., Carpenter, K., Salmon, E. E., & Resnicow, K. (2023) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2023.06.005 · Cited by 11
Design of a randomized controlled trial of smoking cessation medications for alcohol reduction among HIV-positive heavy drinkers and daily smokers in St. Petersburg, Russia
Tindle, H. A., Freiberg, M. S., Gnatienko, N., Blokhina, E. A., Cheng, D. M., Yaroslavtseva, T. V., Bendiks, S., Winter, M. R., Krupitsky, E. M., & Samet, J. H. (2020) · Contemporary Clinical Trials Communications · doi:10.1016/j.conctc.2020.100625 · Cited by 11
Comparison of Levels of Three Tobacco Smoke Exposure Biomarkers in Children of Smokers
Mahabee‐Gittens, E. M., Matt, G. E., Ding, L., & Merianos, A. L. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph182211803 · Cited by 11
Commentary on Graham et al.: Biochemical verification of abstinence in remotely conducted smoking cessation trials should not be a universal design requirement for rigor
Heffner, J. L., & McClure, J. B. (2022) · Addiction · doi:10.1111/add.15803 · Cited by 11
Long-Term Outcomes of a Comprehensive Mobile Smoking Cessation Program With Nicotine Replacement Therapy in Adult Smokers: Pilot Randomized Controlled Trial
Marler, J. D., Fujii, C. A., Utley, M. T., Balbierz, D. J., Galanko, J. A., & Utley, D. S. (2023) · JMIR mhealth and uhealth · doi:10.2196/48157 · Cited by 10
“However, these biomarkers require urine collection and chromatography–mass spectrometry measurement [65].”
Helping pregnant smokers quit: a multi-centre randomised controlled trial of electronic cigarettes versus nicotine replacement therapy
Przulj, D., Pesola, F., Smith, K. M., McRobbie, H. J., Coleman, T. J., Lewis, S., Griffith, C., Walton, R. T., Whitemore, R., Clark, E., et al. (2023) · Health Technology Assessment · doi:10.3310/agth6901 · Cited by 11
Behavior Change Intervention for Smokeless Tobacco Cessation Delivered Through Dentists in Dental Settings: A Pragmatic Pilot Trial
Rasool, S., Holliday, R., Khan, Z., Dobbie, F., & Bauld, L. (2023) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntad243 · Cited by 12
“46 The same was noted in the current study as the abstinence rate dropped by 50% with biochemical verification.”
Background
Association Between Secondhand Smoke Exposure and Nonalcoholic Fatty Liver Disease in the General U.S. Adult Nonsmoker Population
Liu, E., Li, Q., Pan, T., & Chen, Y. (2023) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntad249 · Cited by 10
Effect of 3 months and 12 months of financial incentives on 12‐month postpartum smoking cessation maintenance: A randomized controlled trial
USSHER, M. H., Best, C. S., Lewis, S., McKell, J., Coleman, T. J., Cooper, S. E., Orton, S., & Bauld, L. (2024) · Addiction · doi:10.1111/add.16487 · Cited by 10
Effectiveness of the Offer of the Smoke Free Smartphone App Compared With No Intervention for Smoking Cessation: Pragmatic Randomized Controlled Trial
Jackson, S. E., Kale, D., Beard, E., Perski, O., West, R., & Brown, J. (2024) · Journal of Medical Internet Research · doi:10.2196/50963 · Cited by 13
“While biochemical verification is widely considered the gold standard for evaluating cessation outcomes [22,32], the Society for Research on Nicotine and Tobacco Subcommittee on Biochemical Verification has advised that in large-scale population-based trials such as this one, where face-to-face…”
Interventions to change vaping harm perceptions and associations between harm perceptions and vaping and smoking behaviours: A systematic review
East, K. A., Simonavičius, E., Taylor, E. V., Brose, L. S., Robson, D., & McNeill, A. D. (2025) · Addiction · doi:10.1111/add.70129 · Cited by 9
“While many biomarkers exist for smoking [118], none are validated for vaping [119] and no measures of vaping or nicotine harm perceptions have been comprehensively evaluated psychometrically.”
3D in vitro co-culture disc for spatiotemporal image analysis of cancer–stromal cell interaction
Takahashi, H., & Kikuchi, Y. (2021) · Biomaterials Science · doi:10.1039/d1bm00629k · Cited by 10
Pilot randomized trial of cognitive-behavioral treatment plus contingency management for quitting smoking and weight gain prevention among smokers with overweight or obesity
García–Fernández, G., Krotter, A., Pérez, Á. G., Diego, G. A., & Secades‐Villa, R. (2022) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2022.109477 · Cited by 9
Geometric Mean Serum Cotinine Concentrations Confirm a Continued Decline in Secondhand Smoke Exposure among U.S. Nonsmokers—NHANES 2003 to 2018
Caron, K. T., Zhu, W., Bernert, J. T., Wang, L., Blount, B. C., Dortch, K., Hunter, R. E., Harmon, T. L., Akins, J. R., Tsai, J., et al. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19105862 · Cited by 10
Self-citation
Development of an Ultra-High Performance Liquid Chromatography method for the simultaneous mass detection of tobacco biomarkers in urine
Colsoul, M., Goderniaux, N., Vanpee, D., & Galanti, L. M. (2022) · Journal of Chromatography B · doi:10.1016/j.jchromb.2022.123476 · Cited by 10
Post-Cessation Weight Gain among Smokers with Depression Predicts Smoking Relapse
Krotter, A., Diego, G. A., Pérez, Á. G., García–Fernández, G., & Secades‐Villa, R. (2023) · Journal of Dual Diagnosis · doi:10.1080/15504263.2023.2192683 · Cited by 9
High Cotinine and Healthcare Utilization Disparities Among Low-Income Children
Merianos, A. L., Jandarov, R., & Mahabee‐Gittens, E. M. (2020) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2020.06.018 · Cited by 10
Ongoing tobacco use in women who experience homelessness and unstable housing: A prospective study to inform tobacco cessation interventions and policies
Riley, E. D., Delucchi, K., Rubin, S., Weiser, S. D., Vijayaraghavan, M., Lynch, K. L., & Tsoh, J. Y. (2021) · Addictive Behaviors · doi:10.1016/j.addbeh.2021.107125 · Cited by 11
Hair and nail nicotine levels of mothers and their infants as valid biomarkers of exposure to intrauterine tobacco smoke
Go, M., Al‐Delaimy, W. K., Schilling, D., Vuylsteke, B., Mehess, S., Spindel, E. R., & McEvoy, C. T. (2021) · Tobacco Induced Diseases · doi:10.18332/tid/143209 · Cited by 10
Interventions to prevent or cease electronic cigarette use in children and adolescents
Barnes, C., Turon, H., Hall, A. E., Bialek, C., McCrabb, S., Hodder, R. K., Yoong, S. L., Stockings, E., Agyei, D. D., Mantach, S., et al. (2022) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd015511 · Cited by 10
Immediate, Short-term, Medium-term, and Long-term effects of Acceptance and Commitment Therapy for Smoking Cessation: A Systematic Review and Meta-Analysis
Kwan, Y. K., Lau, Y., Ang, W. W., & Lau, S. T. (2024) · Nicotine and Tobacco Research · doi:10.1093/ntr/ntad145 · Cited by 9
Validation of Urinary Thiocyanate as a Robust Biomarker of Active Tobacco Smoking in the Prospective Urban and Rural Epidemiological Study
Mathiaparanam, S., Gill, B., Sathish, T., Paré, G., Teo, K. K., Yusuf, S., & Britz‐McKibbin, P. (2023) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntad027 · Cited by 10
Cost-Effectiveness of a Comprehensive Primary Care Smoking Treatment Program
Mundt, M. P., McCarthy, D. E., Baker, T. B., Zehner, M. E., Zwaga, D., & Fiore, M. C. (2023) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2023.10.011 · Cited by 10
Implementation, enrollment, and engagement in an opt‐out telehealth pharmacist‐assisted tobacco treatment program for patients seen in oncology outpatient clinics
Cummings, K. M., Toll, B. A., Talbot, V., Roberson, A., Wilson, D., Dunlap, M., Ware, E. C., Palmer, A. M., Bliss, A. A., Anokye, V. S., et al. (2024) · Cancer · doi:10.1002/cncr.35291 · Cited by 9
The Efficacy of the SinHumo App Combined With a Psychological Treatment to Quit Smoking: A Randomized Clinical Trial
López‐Durán, A., Martínez-Vispo, C., Suárez-Castro, D., Barroso-Hurtado, M., & Becoña, E. (2024) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntae053 · Cited by 13
“20,21 Nicotine and Tobacco Research , 2025, Vol. 27, No. 3”
NHANES-based analysis of the correlation between leisure-time physical activity, serum cotinine levels and periodontitis risk
Fu, H., Zhang, D., & Li, Y. (2024) · BMC Oral Health · doi:10.1186/s12903-024-04141-9 · Cited by 9
“Considering the underestimation of smoking when self-reporting smoking status [40], the cotinine test provides a quantitative and accurate reflection of the body’s short-term tobacco exposure level and is suitable for assessing smoking status and intensity [41, 42].”
Background
Implementation of an “opt-out” tobacco treatment program in six hospitals in South Carolina
Cummings, K. M., Talbot, V., Roberson, A., Bliss, A. A., Likins, E., Brownstein, N. C., Stansell, S., Adams-Ludd, D., Harris, B., Louder, D. S., et al. (2024) · BMC Health Services Research · doi:10.1186/s12913-024-11205-7 · Cited by 9
“Biochemical validation of smoking status represents a potential solution to improving the accuracy of smoking status assessment but was not done as part of screening process because it would have added additional costs to the program [27].”
Background
The “Organic” Descriptor and Its Association With Commercial Cigarette Health Risk Expectancies, Subjective Effects, and Smoking Topography: A Pilot Human Laboratory Study
Pearson, J., Watanabe, M., Sanchez, J., Mann, S., Drake, C. S., & Mercincavage, M. (2021) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntab151 · Cited by 9
Non-pharmacological interventions for tobacco cessation: A systematic review of existing practices and their effectiveness
Saroj, S. K., & Bhardwaj, T. (2022) · Monaldi Archives for Chest Disease · doi:10.4081/monaldi.2022.2229 · Cited by 9
Minor Tobacco Alkaloids as Biomarkers to Distinguish Combusted Tobacco Use From Electronic Nicotine Delivery Systems Use. Two New Analytical Methods
Jacob, P., Chan, L., Cheung, P., Bello, K., Yu, L., Helen, G. S., & Benowitz, N. L. (2022) · Frontiers in Chemistry · doi:10.3389/fchem.2022.749089 · Cited by 9
Self-citation
Tobacco Smoke Exposure and Sleep Duration among U.S. Adolescents
Merianos, A. L., Stone, T. M., Mahabee‐Gittens, E. M., Jandarov, R., & Choi, K. (2023) · Behavioral Sleep Medicine · doi:10.1080/15402002.2023.2232498 · Cited by 9
“…of about 16 h and is a measure of recent nicotine exposure that can intermittently occur in any location from products containing nicotine (Benowitz et al., 2020), whereas homes are the most common location of adolescent TSE and a more chronic, major source of exposure (Walton et al.,…”
Background
Contingency management for smoking cessation for individuals with overweight or obesity: A randomized controlled trial
Krotter, A., García–Fernández, G., Pérez, Á. G., Diego, G. A., & Weidberg, S. E. (2024) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2024.111269 · Cited by 10
Specific Relapse Predictors: Could Cognitive-Behavioral Treatment for Smoking Cessation Be Improved?
Martínez-Vispo, C., López‐Durán, A., Senra, C., & Becoña, E. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17124317 · Cited by 9
Acute subjective sensory perceptions predict relative reinforcing effects of smoked nicotine
Karelitz, J. L., & Perkins, K. A. (2021) · Addictive Behaviors · doi:10.1016/j.addbeh.2021.106835 · Cited by 9
Pilot trial of QuitBet: A digital social game that pays you to stop smoking.
Bloom, E. L., Japuntich, S. J., Pierro, A., Dallery, J., Leahey, T. M., & Rosen, J. A. (2021) · Experimental and Clinical Psychopharmacology · doi:10.1037/pha0000487 · Cited by 10
Rate of smoking cessation and factors associated with successful quit smoking in Seremban District of Malaysia
Zamzuri, M. ‘. I. A., Kamarudin, S. A. A., Ariffin, A. H., Ibrahim, A. A., Othman, M. H., Johari, A., Ali, N. K. M., Jetly, K., Rashid, M. F. A., Hassan, M. R., et al. (2021) · Clinical Epidemiology and Global Health · doi:10.1016/j.cegh.2021.100862 · Cited by 9
A Randomized Trial of Nicotine versus No-nicotine E-cigarettes Among African American Smokers: Changes in Smoking and Tobacco Biomarkers
Okuyemi, K. S., Ojo-Fati, O., Aremu, T. O., Friedrichsen, S. C., Grude, L., Oyenuga, M., Shyne, M. T., Murphy, S. E., Hatsukami, D. K., & Joseph, A. M. (2021) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntab212 · Cited by 9
Self-citation
Association of depression symptom level with smoking urges, cigarette withdrawal, and smoking reinstatement: A preliminary laboratory study
Tucker, C. J., Bello, M. S., Weinberger, A. H., D’Orazio, L. M., Kirkpatrick, M. G., & Pang, R. D. (2022) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2022.109267 · Cited by 9

Authors: Benowitz, N. L., Bernert, J. T., Foulds, J., Hecht, S. S., Jacob, P., Jarvis, M. J., Joseph, A., Oncken, C., & Piper, M. E.
Affiliations: University of California, San Francisco (US)
Centers for Disease Control and Prevention (US)
Pennsylvania State University (US)
University of Minnesota (US)
University College London (GB)
University of Connecticut (US)
University of Wisconsin–Madison (US)
Corresponding author: Benowitz, Neal L
ORCID: Benowitz, Neal L
Foulds, Jonathan
Hecht, Stephen S
Jacob, Peyton
Jarvis, Martin J
Joseph, Anne
Oncken, Cheryl
Piper, Megan E
Venue: Nicotine & Tobacco Research
Publisher: Oxford University Press (OUP)
Published: 2019-10-01
Volume: 22
Issue: 7
Pages: 1086-1097
ISSN: 1462-2203 (ISSN-L)
1469-994X
DOI: 10.1093/ntr/ntz132
PMC: PMC7882145
OpenAlex: W2978389675
Cited by: 619
References: 121
Citations by year: 2026: 99 · 2025: 84 · 2024: 107 · 2023: 103 · 2022: 87 · 2021: 79 · 2020: 54 · 2019: 4
FWCI: 6.58
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations: Nicotine & Tobacco Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institutes of Health (CC999999)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
Keywords: tobacco use, smoking abstinence, biomarkers, cotinine, carbon monoxide, electronic cigarettes, NNAL, biological specimen, detection window
MeSH terms: Cigarette Smoking, Carbon Monoxide, Cotinine, Humans, Nicotine, United States, Biomarkers, Smoking Cessation, Tobacco Products

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Biochemical Verification of Tobacco Use and Abstinence: 2019 Update

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