Science of drug testing

Summary

Drug testing is done to ensure the safety of the general public, to maintain standards at schools and places of employment, and to make sure that athletes do not gain unfair advantage through the use of performance-enhancing drugs. The goal of these tests is to detect whether a person has used drugs such as alcohol, marijuana, cocaine, amphetamines, barbiturates, benzodiazepines, lysergic acid diethylamide (LSD), opiates, phencyclidine (PCP), synthetic hormones, and steroids. Commonly used drug tests analyze a person's breath, urine, saliva, sweat, blood, or hair.

Definition and Basic Principles

Drug testing in the workplace and some academic institutions has become commonplace. It has garnered increased attention in the twenty-first century following many high-profile doping cases in athletics. A variety of tests are used to detect elevated levels of the most common drugs that can impair job performance or are illegal to use. The importance of drug testing has continued to increase since the Controlled Substances Act of 1970 placed all regulated drugs into five classifications based on their medicinal value, their potential to harm people, and their likelihood of being abused or causing addiction. Schedule I drugs have no known medical value and are most likely to be abused, while Schedule V drugs have little potential for abuse. These scheduled drugs are called controlled substances because their use, manufacture, sale, and distribution are subject to control by the federal government.

There are two general types of drug testing. Federally regulated drug testing, according to the National Institute on Drug Abuse (NIDA), requires testing for cannabinoids (THC, marijuana, hashish), cocaine, amphetamines, opiates (morphine, heroin, and codeine), and PCP. Nonfederally regulated drug testing is often used to test athletes in various sports for the use of creatine, hormones, steroids, and other performance-enhancing drugs. Additional tests are used to detect barbiturates and alcohol.

Urinalysis is typically used as a preliminary test because it is less expensive and more convenient than the other tests. Saliva tests and breathalyzers are commonly used. Blood tests, although less frequently employed because they are generally more expensive and invasive, are more dependable, as are hair strand tests. A preliminary positive test using urinalysis must be confirmed by diagnostic tests completed in an analytical laboratory setting, which can take several days to complete. These diagnostic tests include the analytical instruments of gas chromatography (GC), mass spectrometry (MS), ion scanning, high-pressure liquid chromatography (HPLC), immunoassay (IA), and inductively coupled plasma spectrometry (ICP-MS).

Background and History

The detection of ingested drugs in various body fluids first sparked the interest of ancient alchemists. In 1936, Rolla N. Harger of Indiana University patented the Drunkometer, a breath test to measure a person's level of alcohol intoxication. In 1954, Robert F. Borkenstein of Indiana University invented the breathalyzer, which had the benefit of greater portability, to measure blood-alcohol content. However, it was not until the widespread use of recreational drugs in the 1960s that the National Institute of Drug Abuse was established to monitor drug use. With its creation, federal funding became available to researchers to develop drug testing methods, which led to rapid advances. In 1973, physician Robert L. DuPont was appointed director of the National Institute of Drug Abuse. As director, DuPont implemented using the urine test and further developed immunoassays to test for several controlled substances.

In 1981, an airplane crashed on the USS Nimitz, and the investigation into the incident revealed drug use to be a contributing factor. As a result, the United States (US) Navy began random drug testing of all active-duty personnel in 1982. In the 1980s, the US Department of Transportation began testing all of its employees. In September 1986, President Ronald Reagan signed Executive Order 12564, making drug testing mandatory for federal employees and all employees in safety-sensitive positions, such as employees in the aviation and nuclear power industries. The National Institute of Drug Abuse extended this mandatory testing to include truck drivers working in the petroleum industry. This testing has come to be regulated by the Substance Abuse and Mental Health Services Administration (SAMHSA), part of the US Department of Health and Human Services.

How It Works

Because of the commercial availability of so many masking agents, the most effective drug testing occurs when the subject has had no previous notification. Thus, random drug testing is very effective and has become common in the workplace, schools, and for athletes. The National Collegiate Athletic Association and the National Football League provide only one to two days' notice before drug testing, and the United States Olympic Committee has a no-notice policy for drug testing.

The first commonly available drug testing method was the breathalyzer, followed by urinalysis. The usage of saliva tests continues to increase, while sweat tests remain the least-used testing method. Blood tests require additional medical staff and are also the most invasive testing method; therefore, although they are very accurate, they are not as commonly used as urinalysis. Hair tests are very accurate but do not detect drug use in the last four to five days. They can, however, detect substance use for an extended period preceding the test. In terms of validity for legal purposes, any of these preliminary, or screening, tests must be confirmed by an analytical technique, most often gas chromatography/mass spectrometry, performed by trained personnel within a diagnostic laboratory.

Breath. Borkenstein received a patent in 1958 for the breathalyzer, which determines an individual's blood-alcohol content (BAC) from a breath sample. The ethanol in the breath of an individual reacts with the dichromate ion, which has a yellow-orange color, in the presence of acid to form the green chromate ion. This color change from pale orange to green can easily be observed. Most states and the District of Columbia have laws that forbid a person to drive with a BAC of 0.08 percent or greater, a level at which the individual is judged to be legally impaired. Utah is one state where the level is even lower.

Urine. Urinalysis became a common method of detecting drugs in the 1980s and has continued to be widely used. The urine sample is collected and sealed to ensure that it remains tamper-free. It is generally subjected to an immunoassay test first because this test is very fast.

Saliva. Testing of oral fluids is becoming increasingly common because of its convenience for random testing, and it is more resistant to adulteration than urine samples. Saliva testing can detect cocaine, amphetamine, methamphetamine, marijuana, benzodiazepines, PCP, opiates, and alcohol if the substance was ingested between six hours and three days before the test was administered.

Sweat. Although traditionally not considered as useful as the other methods because of the dilute sample obtained, patches that can be worn on the skin and collect samples over several hours are increasingly popular. This method of drug testing is preferred by government agencies such as parole departments and child protective services in which urine testing is not the method of choice.

Blood. Because blood tests are the most invasive and expensive method, requiring additional medical personnel, they are not as widely used as the other tests as a screening method. However, blood testing is very accurate and reliable, so it is often used to confirm a positive result from another type of drug test.

Hair. Hair samples from any part of the body can be used and are extremely resistant to any type of tampering or adulteration. Special fatty esters are permanently formed in the hair as a result of alcohol and drug metabolism, and therefore, this method is very reliable.

Gas Chromatography/Mass Spectrometry (GC/MS). This tandem analytical instrumentation must be done by trained personnel within a laboratory setting and, therefore, is less convenient than the other testing methods. However, it is much more accurate and is used to confirm more rapid, preliminary tests. The gas chromatograph can separate molecules based on their attractive interactions with the material that packs a column. Molecules take varying amounts of time to travel, or elute, from the column, resulting in different retention times or amounts of time retained on the column's packing material. These separated molecules are then ionized in the mass spectrometer, which can produce molecular weight information.

Applications and Products

Drug Test Dips. Test strips, known as drug test dips, dip strips, drug test cards, or drug panels, use a single immunoassay panel to test for several common drugs at once. Specific reactions between antibodies and antigens allow marijuana, cocaine, amphetamine, opiates, and methamphetamine to be detected in urine samples. These assay strips are so easy to use that the staff of many schools, sports clubs, and offices can use them. However, they must be used only as a preliminary test. Positive results should be confirmed using gas chromatography/mass spectrometry conducted by an independent diagnostic laboratory.

The test strip is removed from its protective pouch and allowed to equilibrate to room temperature. Meanwhile, a urine sample is obtained in a small cup and also allowed to equilibrate to room temperature. The test strip is dipped vertically, with the arrow on the test strip pointing down into the sample, and remains immersed in the urine sample for ten to fifteen seconds. Then, the test strip is removed from the urine sample and placed on a flat, nonabsorbent surface. After five minutes, the test strip is checked for the appearance of any horizontal lines. The appearance of a colored line in the control region of the dip strip and a faded color line in the test region of the dip strip indicates a negative test and that the concentration of a drug is too low to be detected. If only one line appears in the control region, with no line visible in the test region, then the test is considered positive for the presence of drugs. The test is considered invalid if only one line appears in the test region or no line appears. An invalid test usually results from either not following the procedure correctly or not using a large enough urine sample.

The test strips for marijuana use a monoclonal antibody to detect levels of THC, the active ingredient in marijuana, in excess of 50 nanograms per milliliter (ng/ml), the level recommended by SAMHSA. Methamphetamine can be detected in urine samples for three to five days after usage by using a test strip equipped with a monoclonal antibody. A positive test indicates a level in excess of 1,000 ng/ml. A test strip detects the major metabolite of cocaine, benzoylecgonine, for up to twenty-four to forty-eight hours after use. Morphine in excess of 2,000 ng/ml can also be detected by using a test strip containing a specific antibody. Morphine is the primary metabolite product of heroin and codeine.

Kits. Drug tests used for fast, preliminary screening include easy-to-use kits that can test samples of urine, saliva, breath, hair, or sweat. Of these tests, the hair test for drugs is considered the most accurate but is still considered to be a preliminary test. To confirm preliminary results or to obtain results for legal purposes, a sample of saliva or urine must be sent to a laboratory when a more reliable test such as GC/MS must be performed. It can take three to seven days to obtain the results. Urine drug test kits are less expensive than other tests, provide instantaneous results, and are easy to store. However, because of variations in metabolism rate, there can be a three-day to one-month detection window, making these tests easier to adulterate than the saliva, hair, sweat, or blood tests.

Adulteration of Specimens. Adulteration generally refers to intentional tampering with a urine sample, and certain substances can be added to urine to create a false-negative test result. Adulteration of urine samples is a common problem because four types of masking products—dilution substances, synthetic urine, cleaning substances, and adulterants—are readily available. More than four hundred readily available commercial products can mask urine samples. Dilution substances, including diuretics, lower the concentration of a drug in a sample. An individual can either ingest one of these substances before submitting a urine sample or add the substance directly to the urine sample. Synthetic and dehydrated human urine can be bought and submitted for testing. There exists copious advice on the Internet as to how to keep this urine at body temperature so as not to arouse suspicion. An individual can also purchase a cleaning substance, such as an herbal supplement, for $30 to $70 and ingest the substance before submitting a sample. The herbal supplement reacts chemically with the drug to essentially nullify its active ingredient. Adulterants are chemicals that can react with the drugs, but these are actually added to the sample rather than ingested by the individual.

Methods to Detect Adulteration. Several methods can be used to detect the use of some type of adulterant. If the specific gravity of urine is outside the normal range of 1.003 and 1.030, then the sample may have been diluted. Another indication of adulteration via dilution is to test the level of creatine. If the level is too low (less than 5 milligrams, or mg, per deciliter) then dilution took place. Oxidants, such as pyridinium chlorochromate (PCC), bleach, or hydrogen peroxide, can react chemically with the drug to essentially nullify it. One commonly sold PCC adulterant is called Urine Luck. Tests can also detect the presence of any type of additional oxidant. If the pH (acidity-alkalinity) value of the urine is outside the normal range of 4.5 to 8.0, then an adulterant was added. Two common adulterants are sold under the names of Stealth or Klear, and these react chemically with drugs in the urine by oxidizing the active ingredient in marijuana. Another chemical reaction occurs when an adulterant called Clear Choice or Urine Aid prevents enzyme activity in the test, which results in the presence of glutaraldehyde, which causes a false negative. Among the states that have passed laws to prevent the sale of masking agents are Florida, South Carolina, North Carolina, New Jersey, Maryland, Virginia, Kentucky, Oklahoma, Nebraska, Illinois, Pennsylvania, and Arkansas.

Careers and Course Work

An interest and aptitude for biology, chemistry, and quantitative classes are important prerequisites to pursuing a career in drug testing. Additional required characteristics include the ability to solve problems, pay close attention to detail, work under pressure, have good manual dexterity, and have normal color vision. Depending on the requirements of the state of residence, a person needs a certificate or license or an associate's degree in biology, chemistry, or medical technology to be employed as a clinical laboratory technician or medical technician. Specific information regarding certification can be obtained from the board of registry of the American Association of Bioanalysts and the National Accrediting Agency for Clinical Laboratory Sciences. Typical job duties involve drug sample collection and storage and operation of automated analyzers, often wearing protective gloves and safety glasses.

A Bachelor's degree is required to work as a technologist or scientist and earn a higher salary of about $80,000. In addition to a higher salary, a Bachelor's degree allows a person to take on more responsibility and possibly advance into supervisory and managerial positions. The ideal Bachelor's degree is in medical technology, which requires courses in chemistry, biology, microbiology, statistics, computers, and mathematics. To pursue research or become a laboratory director, a Master's or Doctoral degree is necessary. Employment in the drug testing field grew at the rate of 17.4 percent through 2022 due to increased consumption of drugs and alcohol, according to the US Department of Labor. Typical employers include forensic science laboratories, research and development laboratories, and quality assurance laboratories in industry, government, schools, or hospitals.

Social Context and Future Prospects

SAMHSA, part of the US Department of Health and Human Services, regulates mandatory testing. This required testing does not yet test for semisynthetic opioids, such as oxycodone, oxymorphone, and hydrocodone, which are often used to relieve pain but have the potential to be abused. However, many employers, athletic organizations, and schools test for these drugs, and ongoing research is directed toward increasing the convenience and reliability of methods of detecting these drugs. Because so many masking agents are readily available, random testing without prior notification is the most effective method, although it is not without controversy. Schools are increasingly performing random drug testing, often leading to protests that the tests are an invasion of privacy and a violation of Fourth Amendment rights.

Drug testing has become increasingly common in many occupational fields that affect public health and safety. For example, the Omnibus Transportation Employee Testing Act of 1991 by the US Department of Transportation emphasized drug and alcohol testing for commercial vehicle employees. 

Organizations such as the International Olympic Committee, Major League Baseball, National Collegiate Athletic Association, National Basketball Association, and National Football League monitor athletes for the use of more than one hundred anabolic-androgenic steroids. Efforts are being made to eliminate the use of performance-enhancing drugs in all sports. The International Olympic Committee led a collective initiative to create the World Anti-Doping Agency (WADA) in Switzerland in 1999. WADA created a code to standardize regulations and procedures in all sporting countries and keeps a list of prohibited substances. Banned substances include anabolic steroids, hormones, masking agents, stimulants, narcotics, cannabinoids, glucocorticosteroids, and, for some sports, alcohol and beta-blockers during competition. Methods of enhancing oxygen transfer (such as blood doping) and gene doping are also forbidden. The UNESCO International Convention Against Doping in Sport, which came into force in 2007, is a global treaty designed to help governments align their policies with the WADA code. No events brought more attention to the use of banned substances in sports than the exposing of doping scandals in men’s cycling and Major League Baseball. In cycling, a large majority of the sport, including its top athletes, were implicit in the use of banned substances. In baseball, several players, in conjunction with a laboratory in the Bay Area of California, dominated the sport by using performance-enhancing substances that could not be detected by standard drug testing technology. Doping scandals also plagued track and field.

As the twenty-first century progressed, technology advanced, and critical lessons were learned from high-profile drug testing scandals. Fingerprint-based drug testing, which analyzes sweat in fingerprints to detect drugs, increased during the COVID-19 pandemic in 2020-2021, as did oral fluid testing. Both were non-invasive and required less time than many other tests. Sweat patch technology and hair follicle testing promised a more comprehensive view of a patient’s substance abuse timeline. As marijuana became legal in many US states, cannabis breathalyzers were developed and worked in much the same way as their alcohol counterparts. 

Bibliography

“BAC Limit by State 2024.” World Population Review, 2024, worldpopulationreview.com/state-rankings/bac-limit-by-state. Accessed 31 May 2024.

“Cannabis Breathalyzer Advances New Era in Drug Testing Technology.” Hound Labs, 12 Oct. 2023, houndlabs.com/2023/10/12/cannabis-breathalyzer-advances-new-era-in-drug-testing-technology. Accessed 31 May 2024.

"Drug Screening Market by Product (Consumables, Urine Testing Devices, Analytical, Breathalyzer, Chromatography) & Services, Sample Type (Urine, Breath), End User (Workplace, Laboratories, Criminal Justice, Hospitals): Global Forecast to 2029." Market and Markets, 2024, www.marketsandmarkets.com/Market-Reports/drug-alcohol-screening-market-162987773.html, Accessed 31 May 2024.

Jenkins, Amanda J., and Bruce A. Goldberger, eds. On-Site Drug Testing. Totowa, N.J.: Humana Press, 2002.

Karch, Stephen B., ed. Workplace Drug Testing. Boca Raton, Fla.: CRC Press, 2008.

Liska, Ken. Drugs and the Human Body with Implications for Society. Upper Saddle River, N.J.: Pearson/Prentice Hall, 2004.

Mur, Cindy, ed. Drug Testing. Farmington Hills, Mich.:Greenhaven Press/Thomson Gale, 2006.

Pascal, Kintz. Analytical and Practical Aspects of Drug Testing in Hair. Boca Raton, Fla.: CRC Press, 2006. Print.

Thieme, Detlef, and Peter Hemmersbach. Doping in Sports. Berlin: Springer, 2010.

“Workforce Drug Test Positivity Climbs to Highest Level in Two Decades, Finds Quest Diagnostics Drug Testing Index Analysis.” Quest Diagnostics Newsroom, 30 Mar. 2022, newsroom.questdiagnostics.com/2022-03-30-Workforce-Drug-Test-Positivity-Climbs-to-Highest-Level-in-Two-Decades,-Finds-Quest-Diagnostics-Drug-Testing-Index-Analysis. Accessed 31 May 2024.