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Test ID: NICOU    
Nicotine and Metabolites, Urine

Useful For Suggests clinical disorders or settings where the test may be helpful

Monitoring tobacco use

 

Monitoring replacement therapy to verify that it is adequate

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Tobacco use is the leading cause of death in the United States. Nicotine, coadministered in tobacco products such as cigarettes, pipe, cigar, or chew, 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 the basis for addiction for drugs of abuse.

 

Nicotine is rapidly metabolized in the liver to cotinine, exhibiting an elimination half-life of 2 hours. Cotinine exhibits an apparent elimination half-life of 15 hours. Patients using tobacco products excrete nicotine in urine in the concentration range of 1,000 to 5,000 ng/mL. Cotinine accumulates in urine in proportion to dose and hepatic metabolism (which is genetically determined); most tobacco users excrete cotinine in the range of 1,000 to 8,000 ng/mL. Urine concentrations of nicotine and metabolites in these ranges indicate the subject is using tobacco or is receiving high-dose nicotine patch therapy.

 

In addition to nicotine and metabolites, tobacco products also contain other alkaloids that can serve as unique markers of tobacco use. Two such markers are anabasine and nornicotine. Anabasine is present in tobacco products, but not nicotine replacement therapies. Nornicotine is present as an alkaloid in tobacco products and as a metabolite of nicotine. The presence of anabasine >10 ng/mL or nornicotine >30 ng/mL in urine indicates current tobacco use, irrespective of whether the subject is on 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 exhibit urine nicotine values <30 ng/mL, cotinine <50 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 has been observed to accumulate up to 20 ng/mL from passive exposure. Neither anabasine nor nornicotine accumulates from passive exposure.

 

Tobacco users engaged in programs to abstain from tobacco require support in the form of counseling, pharmacotherapy, and continuous encouragement. Occasionally, counselors may elect to monitor abstinence by biochemical 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 through self-administration of tobacco. 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 they may experience early in the withdrawal phase. This can be confirmed by measurement of urine nicotine and metabolite concentrations at steady-state (2-3 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.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Non-tobacco user with no passive exposure:

NICOTINE

<2.0 ng/mL

 

COTININE

<5.0 ng/mL

 

ANABASINE

<2.0 ng/mL

 

NORNICOTINE

<2.0 ng/mL

Interpretation Provides information to assist in interpretation of the test results

Urine nicotine in the range of 1,000 to 5,000 ng/mL with cotinine in the range of 1,000 to 8,000 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 indicates a subject on patch therapy who is actively using a tobacco product.

 

Typical findings are as follows:

 

While using a tobacco product:

-Peak nicotine concentration: 1,000 to 5,000 ng/mL

-Peak cotinine concentration: 1,000 to 8,000 ng/mL

-Anabasine concentration: 10 to 500 ng/mL

-Nornicotine concentration: 30 to 900 ng/mL

 

Tobacco user after 2 weeks complete abstinence:

-Nicotine concentration: <30 ng/mL

-Cotinine concentration: <50 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

-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

-Anabasine concentration: <2.0 ng/mL

-Nornicotine concentration: <2.0 ng/mL

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Dale LC, Hurt RD, Hays JT: Drug therapy to aid in smoking cessation. Tips on maximizing patients' chances for success. Postgrad Med 1998;104:75-78, 83-84

2. Moyer TP, Charlson JR, Enger RJ, et al: Simultaneous analysis of nicotine, nicotine metabolites, and tobacco alkaloids in serum or urine by tandem mass spectrometry, with clinically relevant metabolic profiles. Clin Chem 2002;48:1460-1471