Nicotine and Metabolites, Urine

Tobacco use is the leading cause of death in the United States. Nicotine is present in all tobacco products and is an addicting substance that causes individuals to continue use of tobacco despite concerted efforts to quit. Nicotine stimulates dopamine release and increases dopamine concentration in the nucleus accumbens, a mechanism that is thought to be responsible for addiction to drugs of abuse.

Tobacco users engaged in programs to abstain from tobacco can be monitored by measurement of nicotine and metabolites in a random urine specimen to verify abstinence. If results of biologic testing indicate the patient is actively using a tobacco product during therapy, additional counseling or intervention may be appropriate.

Quantification of urine nicotine and metabolites while a patient is actively using a tobacco product is useful to define the concentrations that a patient achieves. Nicotine replacement dose can then be tailored to achieve the same concentrations early in treatment to assure adequate nicotine replacement so the patient may avoid the strong craving that occurs early in the withdrawal phase. This can be accomplished by measurement of urine nicotine and metabolite concentrations 2 to 3 days after replacement therapy is started. Once the patient is stabilized on the dose necessary to achieve complete replacement and responding well to therapy, the replacement dose can be slowly tapered to achieve complete withdrawal.

Individuals using tobacco products excrete nicotine in their urine in the concentration range of 1,000 to 5,000 ng/mL. Nicotine is rapidly metabolized, exhibiting an elimination half-life of 2 hours. It is metabolized in the liver to cotinine and trans-3-hydroxycotinine. Most tobacco users excrete cotinine in the range of 1,000-8,000 ng/mL, and trans-3-OH cotinine in the range of 3,000-25,000 ng/mL. High-dose nicotine patch therapy can also produce concentrations in this range. Cotinine has an elimination half-life of 15 hours, and trans-3-OH cotinine has an elimination half-life of 10 hours.

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. Detection of these alkaloids indicates current tobacco use, irrespective of whether the subject is using nicotine replacement therapy.

Interpretation
Urine nicotine in the range of 1,000-5,000 ng/mL with cotinine in the range of 1,000-8,000 ng/mL and trans-3-OH cotinine in the range of 3,000-25,000 ng/mL indicates the subject is either actively using a tobacco product or on high-dose nicotine patch therapy. The presence of anabasine and nornicotine anabasine >10 ng/mL or nornicotine >30 ng/mL in urine indicates active use of a tobacco product, regardless of whether the individual is using nicotine replacement therapy.

Heavy tobacco users who abstain from tobacco for 2 weeks exhibit urine nicotine values < 30 ng/mL, cotinine < 50 ng/mL, trans-3-OH cotinine < 120 ng/mL, anabasine < 2 ng/mL, and nornicotine < 2 ng/mL.

Passive exposure to tobacco smoke can cause accumulation of nicotine metabolites in nontobacco users. Urine cotinine and trans-3-OH cotinine have each been observed to accumulate up to 20 ng/mL from passive exposure. Neither anabasine nor nornicotine accumulates from passive exposure.

Knowledge of time elapsed between last dose and specimen collection is important for interpretation of test results.

While using a tobacco product:
Peak nicotine concentration: 1,000-5,000 ng/mL
Peak cotinine concentration: 1,000-8,000 ng/mL
Peak trans-3-OH cotinine concentration: 3,000-25,000 ng/mL
Anabasine concentration: 10-500 ng/mL
Nornicotine concentration: 30-900 ng/mL

Tobacco user after 2 weeks complete abstinence:
Nicotine concentration: < 3 0 ng/mL
Cotinine concentration: < 50 ng/mL
trans-3-OH cotinine concentration: < 120 ng/mL
Anabasine concentration: < 2.0 ng/mL
Nornicotine concentration: < 2.0 ng/mL

Nontobacco user with passive exposure:
Nicotine concentration: < 20 ng/mL
Cotinine concentration: < 20 ng/mL
trans-3-OH cotinine concentration: < 50 ng/mL
Anabasine concentration: < 2.0 ng/mL
Nornicotine concentration: < 2.0 ng/mL

Nontobacco user with no passive exposure:
Nicotine concentration: < 2.0 ng/mL
Cotinine concentration: < 5.0 ng/mL
trans-3-OH cotinine concentration: < 50 ng/mL
Anabasine concentration: < 2.0 ng/mL
Nornicotine concentration: < 2.0 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. CPT code is 83887.




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