Cotinine is a chemical compound produced in the body following the intake of nicotine from tobacco products or nicotine replacement therapies. It is the primary breakdown product, or metabolite, of nicotine and serves as the most widely accepted scientific marker for measuring tobacco exposure. Unlike nicotine, which disappears quickly, cotinine remains detectable for a significantly longer period, making it a reliable tool for assessing recent use or exposure. Measuring cotinine allows scientists and healthcare providers to objectively determine an individual’s level of nicotine exposure, whether that exposure came from smoking, chewing tobacco, vaping, or secondhand smoke.
The Origin and Chemistry of Cotinine
The formation of cotinine begins immediately after nicotine enters the bloodstream, a process that occurs mainly within the liver. Nicotine is metabolized by a specific group of liver enzymes known as the cytochrome P450 system, primarily the enzyme CYP2A6. This enzyme converts a large portion of the absorbed nicotine—between 70% and 80%—into cotinine.
Cotinine is the preferred substance for testing because nicotine has a very short half-life; half the amount is eliminated in about one to four hours, causing its concentration to fluctuate rapidly. In contrast, cotinine is chemically stable and possesses a much longer half-life, ranging from 16 to 19 hours. This extended stability ensures cotinine levels remain consistent throughout the day and provides a broader window for detection. The cotinine is then further broken down into other metabolites or excreted by the kidneys.
Why Cotinine is Measured
Cotinine testing is utilized across several fields to objectively measure an individual’s tobacco use status. Healthcare professionals frequently use the test to monitor patients enrolled in smoking cessation programs, verifying abstinence and confirming compliance with treatment goals. Results also help clinicians determine the appropriate dosage for nicotine replacement therapies, such as patches or gums, to manage withdrawal symptoms effectively.
In the financial sector, life and health insurance companies often require cotinine testing as part of the application process to assess an applicant’s health risks and determine premium rates. Cotinine measurement also plays a role in public health and legal contexts, such as assessing exposure to environmental or secondhand smoke. Testing is also employed in medical evaluations before certain surgeries or organ transplants, where tobacco use is a significant factor in recovery risks.
Detection Methods and Timeframes
Cotinine can be measured using several sample types, each offering a different detection window. Blood, collected as serum or plasma, provides an accurate measure of recent exposure, detecting cotinine for one to three days after the last use. Saliva testing is non-invasive and correlates closely with blood concentration, offering a similar detection period of one to three days.
Urine is the most common and cost-effective method, often remaining positive for three to four days, or longer in heavy users. Cotinine concentrations in urine are significantly higher—four to six times greater—than in blood or saliva, making it a highly sensitive medium for detection. For long-term historical exposure, hair follicle testing is used, which can detect cotinine use for up to 90 days. The choice of method depends on the required detection timeframe.
Interpreting Cotinine Test Results
Cotinine test results are reported in nanograms per milliliter (ng/mL), and the numerical value is categorized to indicate the level of nicotine exposure. The threshold used to distinguish between active use and non-use can vary between laboratories and sample types. For non-smokers with virtually no exposure, cotinine levels in serum or saliva are very low, often less than 1 ng/mL.
Individuals exposed to significant secondhand smoke, known as passive smokers, may show levels that range from 1 ng/mL up to 10 ng/mL. Some labs use cut-offs of 2 ng/mL in serum to indicate passive exposure. Active tobacco users, including cigarette smokers and vapers, exhibit much higher concentrations, exceeding 15 to 20 ng/mL in serum or saliva. Heavy daily smokers commonly have cotinine levels that surpass 100 ng/mL, providing a clear distinction from non-users and those with minor environmental exposure. Urine cut-off values are often set higher, sometimes at 50 ng/mL or more, due to the higher concentration of cotinine in that matrix.