An overview: drugs-of-abuse testing in the clinical laboratory today

Many national reference laboratory groups have standardized testing for drugs of abuse in urinalysis screens. This is done not only for the patients’ convenience but to streamline the test methodologies. The most common CPT Code (80101) for drug urinalysis screening tests for amphetamines, barbiturates, benzodiazepines, cocaine (and metabolites), marijuana metabolites, opiates, phencyclidine, and methaqualone.^1,2 Many employers, including several local, state, and federal agencies, utilize these test menus in random drug urinalysis as well as pre-employment screening. Some labs offer the ability to perform additional variations of drugs-of-abuse testing on hair, saliva, blood, and other samples. Urinalysis testing is commonly performed using enzyme immunoassay (EIA) methods and confirmed with gas chromatography/mass spectrophotometry (GC/MS). Alternative samples are commonly tested by GC/MS. These tests identify a wide variety of illegal drugs of abuse as well as some prescription compounds such as morphine, hydrocodone, and Ritalin. However, prescription drug use and abuse is one area that can cause confusion in some laboratory testing scenarios.

Nonmedical use of prescription drugs in a 2010 University of Michigan study indicated 8% had tried Vicodin, 6.5% had tried Adderall, and 5.6% had tried various other tranquilizers. This is not including those who had taken these drugs under orders from a physician. In addition, as of 2010, approximately 16 million Americans reported using a prescription drug for nonmedical reasons in the past year.³ Many of these drugs are detected in common drugs-of-abuse panels. For example, a 2003 study of Adderall (a common drug prescribed for ADD/ADHD) measured amphetamine concentrations in healthy subjects taking standardized doses of Adderall, demonstrating that a positive result was seen up to 47 hours post dose.⁴ Pain relief drugs are the most commonly abused, with approximately 5.1 million Americans reporting use of these drugs for non-medical reasons in 2010.⁵ 

Some people undoubtedly go to great lengths to mask some of these compounds in drug testing, adding chemicals such as household bleach, salt, vinegar, and even eye drops to urine samples in an attempt to adulterate the collection sample. Additionally, consumption of large amounts of fluid prior to providing a urine sample is a common way some individuals attempt to circumvent positive test results. Some of these masking methods have worked in the past; however most of them can now be detected by urine dipstick testing for pH, specific gravity, and other routine methods.⁶ Regardless, there are always new drugs of abuse that are being examined for possible addition to many drug urinalysis profiles. 

An increase in alternative illicit drugs both in the United States and abroad has raised concern among some medical providers. For example, in 2010, 34.8% of 12th graders in the United States surveyed had tried marijuana.³ Some authorities in Europe have stated that in 2010 alone as many as 41 new psychoactive drugs were identified.⁷ Herbal alternatives to marijuana, such as Spice, have garnered publicity in the past several years as claims of “legal marijuana” have been made—in addition to stories in the press claiming that the active ingredients are undetectable. These synthetic cannabinoids are frequently marketed as incense and not for human consumption. 

Many countries have included synthetic cannabinoids in banned substances within the past three to four years. While there is not a current addition to most drugs-of-abuse screens for synthetic cannabinoids, it was reported in December 2013 that the Department of Defense has added synthetic marijuana to random drug testing performed on troops.⁸ Many referral laboratories currently offer specific testing for these compounds. Testing is performed using liquid chromatography/mass spectrophotometry (LC/MS). Commonly Spice testing includes “monohydroxylation either at the N-alkyl side chain, the napthyl moiety or the indole moiety” in order to measure metabolites JWH-018, JWH-073, and RCS-4.⁹

Synthetic cathinones (more commonly called bath salts) have also garnered attention in media as well as medical circles. The parent compound, cathinone, is the active ingredient in the khat plant and has been used as a recreational pharmaceutical in parts of Africa for centuries.⁶ Like Spice, bath salts are marketed as not for human consumption in order to circumvent legal requirements as well as the FDA. These compounds are available via the Internet and are purported to provide a mild euphoria and amphetamine-like effect. These compounds, to include mephedrone and methylenedioxypyrovalerone (MDPV), were banned by the U.S. government in 2012 as a result of media and political discussions. Again, no current testing is included on standard drug urinalyses; however, many larger referral laboratories offer testing by either GC/MS or liquid chromatography for these compounds in urine, by examining peaks for mephedrone and MDPV. 

Salvia divinorum, also called just Salvia or magic mint, was an herb used by Mazatec Indians for centuries in order to facilitate perceived spiritual encounters.⁶ The herb produces mild hallucinogenic effects in some users and has been in the news, with both lawmakers and media weighing in on the legality of this compound. Salvia is currently illegal in 24 states in the U.S. as well as more than a dozen European and South American countries. The active ingredient, salvinorin A, is typically measured by liquid chromatography at many reference laboratories. This method typically can detect concentrations as low as 5 ng/mL of urine.¹⁰ It is not found in the current standard battery of tests performed in random drug urinalysis, but has been gaining ground recently. 

Several other emerging drugs have been identified as possible drugs of abuse to be potentially added to drug urinalysis screens. These compounds include methoxetamine (an analog to ketamine), kratom (a compound derived from Mitragyna speciosa) and piperazine (an antihelminthic that has been shown to produce amphetamine-like effects).⁶ While many of these drugs are currently legal, from a clinical laboratory perspective the ability to identify accurately and quantify these compounds in urine or other samples can be an important consideration. Some other regulatory changes in drugs of abuse can alter the frequency of requests for drugs-of-abuse panels. 

The U.S. Drug Enforcement Administration (DEA), as a result of the Controlled Substances Act, classifies drugs into five categories or schedules. The schedule of many prescription drugs indicates to both law enforcement and the medical community the capability of a prescription or illicit drug to become addictive, its medical use, and what level of control is warranted. These range from Schedule V (low potential for abuse), including Robitussin AC and Lomotil, to Schedule I (no accepted medical use and highly addictive)—e.g, heroin, LSD, and marijuana. As of October 2013 hydrocodone products (most notably Vicodin and Oxycontin) are listed under Schedule III; however, the FDA has announced plans to reclassify these products into Schedule II. While this may not require significant increases in clinical drug testing, the resultant decrease in prescription of these drugs by healthcare providers could make positive test results more significant both to the patient and medical staff. 

As evolution in testing for drugs of abuse continues, it is important for clinical laboratory managers to stay abreast of legal and medical decisions made regarding many of these compounds and what the test screens actually sample. While we do not determine what is important to test for, our ability to provide accurate results for a wider scope of requirements can impact the laboratory’s continued reputation as a reliable healthcare resource.

Maj. Paul R Eden, MT (ASCP), PhD, a member of the MLO Editorial Advisory Board, is Toxicology Program Manager, 711 HPW/RHDJ, Wright Patterson Air Force Base, Ohio.

References

1. LabCorp Test Menu. http://www.labcorp.com. Accessed January 25, 2014.
2. Quest Diagnostics Test Menu. http://www.questdiagnostics.com/testcenter/TestDetail.action?ntc=14635. Accessed January 25, 2014.
3. NIDA Prescription Drug Abuse. http://www.drugabuse.gov/drugs-abuse/commonly-abused-drugs/commonly-abused-prescription-drugs-chart. Accessed January 25, 2014.
4. Cody JT, Valtier S, Nelson SL. Amphetamine enantiomer excretion profile following administration of Adderall. J Anal Toxicol. 2003;27:(7)485-492.
5. NIDA Fact Sheet. http://www.drugabuse.gov/drugs-abuse/commonly-abused-drugs/commonly-abused-drugs-chart. Accessed January  29, 2014.
6. Dasgupta A. The effects of adulterants and selected ingested compounds on drugs-of-abuse testing in urine. Amer J Clin Path. 2007;128(3):491-503. 
7. Rosenbaum CD, Carreiro SP, Babu KM. Here today, gone tomorrow…and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, salvia divinorum, methoxetamine, and piperazines. J Med Toxicol. 2012; 8(1):15-32.
8. Marshall TC. DOD adds synthetic marijuana to random drug testing. US DoD News. December 23, 2013. http://www.defense.gov/news/newsarticle.aspx?id=121345. Accessed January 25, 2014.
9. Hutter M,  Broecker S, Kneisel S, Auwärter V. Identification of the major urinary metabolites in man of seven synthetic cannabinoids of the aminoalkylindole type present as adulterants in ‘herbal mixtures’using LG-MS/MS techniques. J Mass Spec. 2012;47(1):54-65.
10. McDonough PC, Holler JM, Vorce SP, Bosy TZ, Magluilo J Jr., Past MR. The detection and quantitative analysis of the psychoactive component of Salvia divinorum, Salvinorin A, in human biological fluids using liquid chromatography-mass spectrometry. J Ana Toxicol. 2008; 32(6): 417-421.