Clinical Information

This test uses screening techniques that involves immunoassay testing and high-resolution accurate mass spectrometry screening for drugs by class. All positive immunoassay screening results are confirmed by gas chromatography mass spectrometry (GC-MS) or liquid chromatography tandem mass spectrometry (LC-MS/MS), and quantitated, before a positive result is reported.

The following drugs/drug classes are tested by immunoassay and confirmed by GC-MS:

-Barbiturates

-Cocaine

The following drugs/drug classes are tested by immunoassay and confirmed by LC-MS/MS:

-Carboxy-tetrahydrocannabinol

-Ethyl glucuronide

The targeted opioid, benzodiazepine, and stimulant screen portions are performed using LC-MS/MS high-resolution accurate mass and are completed for all opioids, benzodiazepines, and stimulants.

Opioids are a large class of medications commonly used to relieve acute and chronic pain or help manage opioid abuse and dependence. Medications that fall into this class include buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, tapentadol, tramadol, and others. Opioids work by binding to the opioid receptors that are found in the brain, spinal cord, gastrointestinal tract, and other organs. Common side effects for opioids include drowsiness, confusion, nausea, constipation, and, in severe cases, respiratory depression. These are dose dependant and vary with tolerance. These medications can also produce physical and psychological dependence and have a high risk for abuse and diversion, which is one of the main reasons many professional practice guidelines recommend compliance testing in patients prescribed these medications.

Opioids are readily absorbed from the gastrointestinal tract, nasal mucosa, lungs, and after subcutaneous or intermuscular injection. Opioids are primarily excreted from the kidney in both free and conjugated forms. This assay does not hydrolyze the urine sample and looks for both parent drugs and metabolites (including glucuronide forms). The detection window for most opioids in urine is approximately 1 to 3 days with longer detection times for some compounds (ie, methadone).

Benzodiazepines represent a large family of medications used to treat a wide range of disorders from anxiety to seizures and are also used in pain management. With a high risk for abuse and diversion, professional practice guidelines recommend compliance monitoring for these medications using urine drug tests. However, traditional benzodiazepine immunoassays suffer from a lack of cross-reactivity with all the benzodiazepines, so many compliant patients taking either clonazepam (Klonopin) or lorazepam (Ativan) may screen negative by immunoassay but are positive when confirmatory testing is done. The new targeted benzodiazepine screening test provides a more sensitive and specific test to check for compliance to all the commonly prescribed benzodiazepines and looks for both parent drugs and metabolites in the urine.

Stimulants are sympathomimetic amines that stimulate the central nervous system activity and, in part, suppress the appetite. Amphetamine and methamphetamine are also prescription drugs used in the treatment of narcolepsy and attention-deficit disorder/attention-deficit hyperactivity disorder (ADHD). Methylphenidate is another stimulant used to treat ADHD. Phentermine is indicated for the management of obesity. All other amphetamines (eg, methylenedioxymethamphetamine: MDMA) are Drug Enforcement Administration-scheduled Class I compounds. Due to their stimulant effects, the drugs are commonly sold illicitly and abused. Physiological symptoms associated with very high amounts of ingested amphetamine or methamphetamine include elevated blood pressure, dilated pupils, hyperthermia, convulsions, and acute amphetamine psychosis.

Ethyl glucuronide is a direct metabolite of ethanol that is formed by enzymatic conjugation of ethanol with glucuronic acid. Alcohol in urine is normally detected for only a few hours, whereas ethyl glucuronide can be detected in the urine for 1 to 3 days. This procedure uses immunoassay reagents that are designed to produce a negative result when no drugs are present in a natural (eg, unadulterated) specimen of urine; the assay is designed to have a high true-negative rate. Like all immunoassays, it can have a false-positive rate due to cross-reactivity with natural chemicals and drugs other than those they were designed to detect. The immunoassay also has a false-negative rate to the antibody's ability to cross-react with different drugs in the class for which it is being screened.

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 approximately 15 to 19 hours. Patients using tobacco products excrete nicotine in urine in the concentration range of 1000 to 5000 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 1000 to 8000 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 greater than 10 ng/mL or nornicotine greater than 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 below 30 ng/mL, cotinine values below 50 ng/mL, anabasine levels below 2 ng/mL, and nornicotine levels below 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.

This test is intended to be used in a setting where the test results can be used to make a definitive diagnosis.