Focus on Alcohol & Drug Abuse: Ensuring Validity in Urine Drug Testing

The DSM-IV distinguishes 11 categories of abusable substances, including amphetamines; cannabis; cocaine; hallucinogens; inhalants; opioids; phencyclidine (PCP); sedatives, hypnotics, and anxiolytics; alcohol; caffeine; and nicotine. Despite this, many tests screen only for marijuana, cocaine, opioids, amphetamines, and PCP—the "NIDA five" (after the National Institute on Drug Abuse). Although these substances are the most frequently tested for, no industry standards exist. Terms like "comprehensive drug screen," "routine drug screen," and "standard drug screen" are not used consistently by different laboratories and test manufacturers. Additionally, it is important to note that several substances—notably methylenedioxymethamphetamine (MDMA, or "Ecstasy"), oxycodone, hydrocodone, buprenorphine, and clonazepam—are not included in many drug screens and must be ordered separately. Thus one of the most readily remedied sources of inaccuracy in result interpretation is the use of insufficiently broad tests.

Methods of urine drug analysis fall into two general categories—screening assays and confirmatory tests—although some methods of analysis are used for either purpose.

As noted above, some individuals may be motivated to avoid detection of their drug use. Methods for avoiding detection of substance use ("tampering") include dilution of the sample with water or other liquids, substitution with a "clean" or synthetic urine specimen, and adulteration with other chemicals ( 11 ). Information on avoiding detection is readily available on the Internet.

To ensure integrity of testing results, mandatory guidelines for collecting and checking urine in federal workplace drug testing programs have been established ( 12 ). Although these guidelines are not mandatory in clinical contexts, they do represent a gold standard.

Several characteristics of urine may indicate whether the sample has been adulterated, including pH, temperature, creatinine, specific gravity, and human immunoglobulin (IgG) levels. In a healthy volunteer, urine temperature is expected to be 90°F to 100°F within several minutes of producing a sample. Temperatures outside this range suggest substitution. Similarly, the creatinine level is expected to be greater than or equal to 20 ppm. A creatinine level below this threshold suggests dilution, either directly or through excessive fluid ingestion. In a healthy volunteer, a urine specimen is expected to have a specific gravity level ≥1.003 and a pH level between 3 and 11. A pH or specific gravity level outside of these ranges may suggest chemical adulteration. Finally, IgG concentrations <.5 <g/ml suggest either substitution or dilution. Commonly available chemical adulterants include glutaraldehyde, pyridium chlorochromate, and nitrites ( 11 ). Tests for these chemicals may be performed by commercial laboratories, and "dipstick" devices to perform on-site screens are also commonly available.

In addition to the above integrity checks, other precautions, such as eliminating water sources, prohibiting outer garments and personal belongings from the collection room, having subjects wash their hands, and direct observation of the specimen collection, may also be useful ( 12 ).

Chain-of-custody procedures refer to the means by which a specimen is identified and associated with a specific individual throughout the collection, transport, storage, analysis, and reporting process. Chain-of-custody procedures may vary according to context and laboratory, but failure to implement and ensure accurate procedures poses a significant source of error. For details on implementing valid chain-of-custody procedures, the reader is referred to Substance Abuse and Mental Health Services Administration's Mandatory Guidelines for Federal Workplace Drug Testing Programs ( 12 ).

A number of factors that may contribute to a clinical false-negative result in urine drug testing include substance of interest; analytic technique used; interactions between time frame, substance, and use level; and violation of sample integrity and chain of custody. To ensure the accurate interpretation of urine drug testing, it is important to consider the following topics.

• Are the substances of interest included in the test? Because no standards for terms such as "routine" or "comprehensive" exist, it is important to ensure that the analyses performed will detect the specific substances of interest. Requesting a category of drug test is insufficient.

• Will the requested test provide the desired information? Screening procedures provide qualitative information, whereas confirmatory testing generally provides both qualitative and quantitative information. Confirmatory testing is generally more sensitive and specific, but it is also more expensive. Qualitative screening with confirmatory testing for positive results typically provides the desired information, although some clinical situations require quantitative information.

• Will the testing procedure detect the amount of use within the time frame of interest for a given substance? Urine testing procedures generally only detect relatively recent use. Additionally, the time frame for detection varies by substance (see table showing time frame for detection that is available as an online supplement at ps.psychiatryonline.org), as well as by the frequency and intensity of use. Regular and heavy use may be more easily detected, but intermittent and lighter drug use may be missed.

• Has the sample been diluted, substituted, or adulterated? These are methods used to falsify test results. Proper collection techniques, confirmation of pH, temperature, specific gravity, creatinine, and IgG levels as well as checks for adulterants, including glutaraldehyde, potassium chlorochromate, and nitrates, should be performed whenever tampering is suspected.

• Have accurate chain-of-custody procedures been implemented and followed? Ensuring that a specimen has not been mistakenly or intentionally switched with the specimen of another individual is fundamental to obtaining a valid result.

Opportunities for additional training exist. The Medical Review Officer Certification Council is a physician-based nonprofit board offering certification to physicians who complete a two-day training course and pass an examination ( 13 ). Certification is required for physicians who supervise government-mandated workplace drug-testing programs, but physicians in primary care are less likely to have completed this training. Workshops are also offered by professional societies. The degree to which the validity of urine testing is affected by procedural shortcomings is not known. However, research suggests that further dissemination of the means to ensure validity of these procedures is warranted, because it appears that some physicians are inconsistent when ordering tests, fail to use recommended collection techniques, and do not possess sufficient knowledge to accurately interpret these tests ( 2 ).

The process of obtaining a valid urine drug test result is deceptively complex and affected by several factors, including the substance of interest, test methodology, pharmacokinetics, chain-of-custody procedures, and intentional tampering. It is important to consider all of these factors when conducting urine drug tests.

This work was supported in part by grants K24-DA-022288 and R01-DA-15968 from the National Institute on Drug Abuse.

The authors report no competing interests.

All the authors except for Dr. Levy are affiliated with the McLean Hospital Alcohol and Drug Abuse Treatment Program, 115 Mill St., Belmont, MA 02478 (e-mail: [email protected]). Dr. Jaffee and Dr. Weiss are also with the Department of Psychiatry, Harvard Medical School, Boston. Dr. Teter is also with the School of Pharmacy, Northeastern University, Boston. Dr. Levy is with the Division on Addictions and the Department of Pediatrics, Harvard Medical School, Boston. Shelly F. Greenfield, M.D., M.P.H., served as editor of this column.