Evaluation and Clinical Implications of Biomarkers of Electronic Cigarette Use

Graduation Date


Document Type

Master's Thesis

Degree Name

Master of Science

Department or Program

Clinical Laboratory Sciences

Department or Program Chair

Mary Sevigny, PhD

First Reader

Maciej L. Goniewicz, PharmD, PhD


Significance: Recently, new nicotine-delivery products called electronic cigarettes or e-cigarettes have gained a considerable popularity in the US. Cotinine is a nicotine metabolite excreted with urine and it is a common biomarker used to verify patient’s smoking status in clinical settings. However, cotinine is a biomarker that is selective for all nicotine-containing products and does not distinguish between tobacco cigarette smoking and e-cigarette use. The second biomarker commonly used in clinical trials is called NNAL and it is tobacco-specific. In this pilot study, the simultaneus use of both biomarkers were evaluated to verify e-cigarette use.

Materials and Methods: Urine samples were collected from 4 groups of patients that reported: 1) smoking tobacco cigarettes, 2) using e-cigarette, 3) using both tobacco and electronic cigarettes (so called ‘dual use’), and 4) not using any nicotine product (control). Urine cotinine and NNAL were measured in 180 samples (approx. 45 per group) using LC-MS/MS. The concentration ranges of each biomarker were determined for each group. I have proposed cut-off values for each biomarker that will distinguish between tobacco smokers and e-cigarette users.

Results: The following cut-off values were proposed: 1) tobacco smokers and dual users: cotinine ≥10ng/ml and NNAL≥25pg/ml; 2) e-cigarette users: cotinine≥10ng/ml and NNAL<25pg/ml, and 3) non-users: cotinine <10ng/ml and NNAL<25pg/ml.

Conclusions: The use of both cotinine and NNAL biomarkers is an effective measure to verify smoking and confirm e-cigarette use compared to using cotinine or NNAL alone. Synergistic effect of the established cut-off values to both biomarkers enhances demarcation in the smoking status among different population group to specific product of their choice.

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