Nicotine and Metabolites, Urine

Tobacco smoke is a complex mixture of compounds including nicotine, carbon monoxide, tar, hydrogen cyanide, nitrogen oxides, N-nitrosamines, formaldehyde, and benzene. Nicotine is  an addicting substance that causes individuals to continue use of tobacco despite concerted efforts to quit. More than 45 million Americans or 19% of the adult population still smoke tobacco. Smoking is a risk factor for cancer, cardiovascular disease, and pulmonary disease and is the leading cause of preventable death in the United States.

Smoking is also associated with adverse surgical outcomes including impaired wound healing, wound dehiscence, incisional hernia formation, surgical site infection and pulmonary complications. Several mechanisms are responsible for the detrimental effect of smoking on wound healing including vasoconstriction, tissue ischemia, thrombosis, reduced inflammatory response, impaired bacteriocidal activity and alterations of collagen metabolism. Tissue flaps, which have a fragile blood supply, are particularly vulnerable to these smoking-induced reductions in blood flow.

 Studies have shown that patients tend to lie about smoking, with approximately 25% of self-reported nonsmokers testing positive for nicotine metabolites and 50% of smokers under-reporting the amount they smoke. Smoking can be detected by measurement of nicotine and metabolites in a random urine specimen. Urine testing can also be used to monitor compliance of individuals engaged in smoking cessation programs.

Nicotine has a very short elimination half-life of 2 hours because it is rapidly metabolized in the liver to cotinine which has a longer elimination half-life of 15 hours. Active users of tobacco products excrete nicotine in urine in the concentration range of 1,000 to 5,000 ng/mL. and cotinine in the range of 1,000 to 8,000 ng/mL. Urine concentrations of nicotine and cotinine in these ranges may also be seen in individuals receiving high-dose nicotine patch therapy.

In addition to nicotine and its metabolites, tobacco products also contain other alkaloids that can serve as unique markers of tobacco use. Two examples are anabasine and nornicotine, which are present in tobacco products, but not nicotine replacement therapies. The presence of anabasine and nornicotine anabasine greater than 10 ng/mL or nornicotine greater than 30 ng/mL in urine indicates active use of a tobacco product, regardless of whether the individual is using nicotine replacement therapy. The presence of nornicotine without anabasine is consistent with use of nicotine replacement products.

Heavy tobacco users who abstain from tobacco for 2 weeks usually have urine nicotine values less than 30 ng/mL, cotinine less than 50 ng/mL, anabasine less than 2 ng/mL, and nornicotine less than 2 ng/mL.

Passive exposure to tobacco smoke can cause accumulation of nicotine metabolites in nontobacco users. Urine cotinine has been observed to accumulate up to 20 ng/mL from passive exposure. Neither anabasine nor nornicotine accumulates from passive exposure.

Urine reference ranges are:



Reference Range


0-2 ng/mL


0-5 ng/mL


0-2 ng/mL


0-2 ng/mL


Nicotine and its metabolites are measured by Liquid Chromatography-Tandem Mass Spectrometry. Specimen requirement is a 3.0 mL aliquot of urine from a random specimen collected without preservative. 

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