Cotinine is a chemical compound formed when nicotine is processed in the body. It serves as a reliable marker for detecting nicotine exposure, primarily from tobacco products. Its presence indicates nicotine absorption, whether through active use or environmental exposure, making it a key tool for monitoring intake.
Cotinine’s Origin and Purpose
Cotinine is the main metabolite of nicotine, formed when nicotine breaks down in the body. This conversion occurs largely in the liver, with enzyme CYP2A6 playing a central role. Approximately 70-80% of absorbed nicotine transforms into cotinine.
Cotinine is a significant biomarker due to its stability and longer presence compared to nicotine. Nicotine has a short half-life (2-3 hours), making extended exposure detection difficult. Cotinine, however, has a significantly longer half-life (12-20 hours), allowing detection for several days. This extended window makes it a practical indicator for assessing recent nicotine use from tobacco products and nicotine replacement therapies.
How Cotinine is Measured
Cotinine can be measured in various biological samples: urine, blood (serum or plasma), saliva, and hair. Urine samples often yield higher concentrations, sensitive for detecting low-dose exposure. Saliva and blood concentrations are widely used, with saliva levels often correlating closely with blood levels.
Laboratory methods for cotinine detection include immunoassays and gas chromatography-mass spectrometry (GC-MS). Immunoassays (e.g., ELISA) are used for speed and convenience, offering preliminary results. GC-MS is a more precise, sensitive method, confirming immunoassay results and providing quantitative measurements. These techniques allow accurate assessment of cotinine levels across sample types.
Understanding Cotinine Test Results
Cotinine test results are interpreted by understanding what different concentration ranges indicate about nicotine exposure. Undetectable or very low levels (typically below 1 ng/mL in serum) suggest no recent nicotine exposure, characteristic of non-smokers. Secondhand smoke exposure levels range from above 1 ng/mL up to approximately 30 ng/mL, depending on intensity. Some overlap can occur between heavy secondhand smoke exposure and light active smoking.
For active users of tobacco or nicotine products, cotinine levels are significantly higher. Average cotinine levels for adult smokers in the U.S. can exceed 100 ng/mL, with heavy smokers reaching much higher concentrations. A common cutoff to differentiate active tobacco use from non-use or passive exposure is around 4 ng/mL for blood or saliva, though specific values vary by laboratory. The presence of other tobacco alkaloids, like anabasine, helps distinguish active tobacco use from nicotine replacement therapy.
Factors Affecting Cotinine Levels
Several factors can influence an individual’s cotinine levels, even with similar nicotine exposure. Metabolic rates play a role, with genetic variations in the CYP2A6 enzyme affecting nicotine breakdown. Individuals with genetic variations leading to reduced CYP2A6 activity may metabolize nicotine more slowly, resulting in higher, longer-persisting cotinine levels.
The health of an individual’s liver and kidneys also influences cotinine levels. The liver is where most nicotine metabolism occurs, so its health impacts cotinine conversion. The kidneys eliminate cotinine; impaired function can lead to higher concentrations due to slower excretion. External factors, such as nicotine product type and amount, exposure duration, and certain medications, can also affect cotinine metabolism and overall levels.