Nicotine & Metabolites

Indications for Testing

Document tobacco use (to assess compliance with smoking cessation programs and to qualify for certain medical procedures)

Laboratory Testing

Urine testing recommended over serum/plasma to detect chronic use
- Nicotine is metabolized into several compounds that are measurable in urine and serum; analytes are detectable in urine over a longer period of time to differentiate patient as the following
  - Active user
  - Abstinent >2 weeks
  - Passively exposed
  - Unexposed nonuser
- Anabasine in urine indicates patient is actively using a tobacco product
  - Anabasine is not expected in nicotine replacement products
Serum/plasma testing is required when a valid urine specimen cannot be obtained (anuretic or dialysis patient) or to detect recent use (within past 2 weeks)

Tobacco cessation
- Measure urine concentrations of nicotine, cotinine, trans-'3-hydroxycotinine, nornicotine and anabasine
  - Plasma levels cannot differentiate between nicotine patch and tobacco use
Helpful in the following situations
- Compliance with smoking cessation programs
- Candidates for orthopedic surgery and some other surgeries (eg, spinal fusion, wound revision, plastic surgery), pulmonary therapy and organ transplantation
- Identification of patients with unacknowledged tobacco use
Experimental nicotine therapy in cognitive degeneration disorders, (eg, Alzheimer disease, Parkinson disease, and attention deficit/hyperactivity disorder)

Nicotine is extensively metabolized in the liver into the following
- Cotinine – represents 70-80% of metabolized nicotine
  - Mediated by cytochrome P450 system (mainly CYP2A6 and CYP2B6)
- Trans-3'-hydroxycotinine – a metabolite of cotinine
- Nornicotine – a metabolite of nicotine
- Anabasine – minor tobacco alkaloid
  - Check compliance with nicotine replacement therapy
    - Presence of anabasine suggests recent tobacco use or exposure
    - Absenceof anabasine is not definitive evidence that tobacco was not used because anabasine concentrations are expected to vary with tobacco preparations
Plasma half life for nicotine is 0.4-1.5 hours; estimated detection window in urine is 3 days for nicotine and 1 week for cotinine

Use of tobacco products, particularly smoking, is a leading but preventable cause of disease, disability and death.

Epidemiology

Prevalence – 15-20% of adults are nicotine dependent
Sex – M>F

Pathophysiology

Nicotine is found in a variety of plants
Principle source of exposure – tobacco products or nicotine replacement therapy
Extensively metabolized by the liver
Absorbed through oral cavity, skin, urinary tract and gastrointestinal tract
Increases heart rate, blood pressure, mobilization of blood sugars and catecholamines

Clinical Presentation

Cancers – lung, larynx, oral and nasal cavity, paranasal sinuses, esophagus, pancreas, liver, stomach, cervix, leukemia (AML, CML, CLL)
Cardiac and neurologic disease – leading cause of coronary disease, stroke
Pulmonary disease – chronic obstructive pulmonary disease (includes chronic bronchitis and emphysema), asthma, respiratory infections, overall decrease in pulmonary function
Pregnancy – difficulty in conceiving, intrauterine growth retardation, low birth weight
Second-hand smoke – a confirmed human carcinogen implicated in pulmonary disease, lung cancer and coronary artery disease in non-smokers

Tests generally appear in the order most useful for common clinical situations

Test name: Nicotine & Metabolites, Urine

ARUP #: 0092356

Methodology: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Use:

Detect nicotine, cotinine, trans-3'-hydroxycotinine, nornicotine and anabasine in urine

Presence of anabasine identifies tobacco use

Distinguish between categories of tobacco exposure and/or use - unexposed non-user passive exposure, abstinence (>2 weeks) and active users

Limitations: Failure to detect anabasine is not definitive evidence of tobacco abstinence; interpretive questions should be directed to laboratory

Test name: Nicotine & Metabolites, Serum or Plasma

ARUP #: 0092361

Methodology: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Use:

Detect and monitor nicotine, cotinine, and trans-3'-hydroxycotinine in serum or plasma

Order when valid urine specimen cannot be obtained (eg, anuretic or dialysis patient)

Limitations:

Does not detect anabasine

Interpretive questions should be directed to laboratory

Guidelines

General

ARUP Institute for Clinical and Experimental Pathology®

McMillin, Gwendolyn A., PhD. Medical Director of Clinical Drug Abuse Testing, Clinical Toxicology and Trace Elements, Co-Medical Director for Pharmacogenomics at ARUP Laboratories; Assistant Professor of Pathology (Clinical), University of Utah

Comprehensive Review: December 2011
Last Update: December 2011

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