What's in the Cup: A Urine Drug Testing Primer

By: Jody Lutz and Mario Ramirez, MD

Reading Time: 9 minutes

Date: 04/24/2018

Filed Under: Opioid Prescribing Guidelines, Urine Drug Testing

Urine drug testing (UDT) is a critical tool for patients on chronic opioid therapy.  It is also one of the most misunderstood. 

As most states have updated their opioid prescribing guidelines over the past two years, nearly every one now includes a requirement to conduct urine drug screening in certain populations. Unfortunately, many of these recommendations have been developed in isolation with variances across the level of testing to conduct, testing frequency, and guidelines required for medical necessity.

Practices deal with uncertainty about how to address each of these issues when state guidelines may be in conflict with private payer requirements or professional association recommendations. On top of that, testing recommendations by national agencies and the Centers for Medicare and Medicaid Services (CMS) at the initiation of opioid therapy, in risk stratified chronic opioid therapy (COT) patients, and in patients undergoing medication assisted therapy (MAT) for drug addiction may diverge. Many of these concepts are examined in The Philosophy of Urine Drug Testing in Pain Management.

The policies and plans are outlined - but what does it all mean? What does that cup do and what do the results mean? And as the clinician, how do you know which tests to order to remain in regulatory compliance and manage patient risk?

This primer of key terms and concepts will help you better understand the terminology and technology behind medication monitoring and UDT. Here’s a brief overview of what’s in the cup.


The Basics

UDT is a tool utilized by physicians prescribing opioid therapy for pain patients to provide additional clinical information about medication compliance, use of non-prescribed medications, and use of illicit drugs. It is part of the multi-faceted approach to medication monitoring during the Opioid Epidemic age.

Urine Drug Testing in Chronic Pain Management is another good overview resource.

 Urine Drug Testing Sample


Key Testing Terms

Cut Off Level: A numeric value that is set by laboratory, which is the point which separates a test result as being positive or negative. Above the cut off level, the result is positive and below the cut off level the result will be negative. A cut-off is typically chosen that will optimize drug detection but minimize the number of false positive results.

Definitive Testing: In some states, and in some situations, more definitive testing is required than a POCT screen. Definitive drug tests are qualitative or quantitative tests used to identify specific drugs, specific drug concentrations, and associated metabolites. Often referred to as “Confirmatory Testing” this level of testing is performed by mass spectrometry: e.g., gas chromatography with mass spectrometry (GC-MS) or liquid chromatography with tandem-mass spectrometry (LC-MS/MS).

Expected Positive: Test for a prescribed medication that is positive as expected.

Presumptive Testing: Determines the presence or absence of a drug or drug class, not as specific as the definitive methods. Often used as a POCT cup.

Qualitative Testing: Testing with a positive or negative result report.

Quantitative Testing: Testing with a numerical results report value.

Specimen Validity Testing: Does not test for drugs or drug classes but confirms the validity of a specimen by checking pH, creatine, specific gravity, etc. This ensures no additives have been placed in the urine and that synthetic urine was not utilized. In essence, ensuring that a specimen is unadulterated human urine.

Therapeutic Drug Monitoring: Drug testing related to the monitoring of prescription medications, including patients on continuous opioid therapy

Unexpected Negative: Test for a prescribed medication that is unexpectedly negative. If a patient is taking their medication as prescribed, the UDT result should be positive.


Regulatory Bodies

CLIA: Clinical Laboratory Improvement Amendments (CLIA) of 1988 are United States federal regulatory standards that apply to all clinical laboratory testing performed on humans in the United States, except clinical trials and basic research.

COLA: COLA is an independent laboratory accrediting body. The organization is an independent, non-profit accreditor whose education-based program and standards enable clinical laboratories and staff to meet U.S. CLIA 88 and other regulatory requirements.

CAP: The College of American Pathologists (CAP), the leading organization of board-certified pathologists, serves patients, pathologists, and the public by fostering and advocating excellence in the practice of pathology and laboratory medicine worldwide.


Point of Care Testing (POC or POCT)



Point of Care Testing: POCT drug testing is performed outside the clinical laboratory in a location close to the site of care delivery. POC UDTs are inexpensive, provide immediate results, and can detect illicit and addictive prescription drugs for two to five days following their use, with the exception of cannabis which can be detected for a week or more . CLIA-waived drug screening devices consist of enzyme mediated immunoassay cards, dipsticks, cassettes and cups that give a simple positive or negative result. Common urine drug testing device include the 12 panel cup which tests for for amphetamines, barbiturates, benzodiazepines, buprenorphine, cocaine, marijuana, methadone, methamphetamines, opiates, oxycodone, phencyclidine and propoxyphene. Other variations include a test strip for buprenorphine as well. These are the least expensive and easiest to administer urine drug monitoring tools.

The tests are not perfect, however, and the American Academy of Clinical Chemistry examines the pitfalls of Point of Care Urine Drug Screening in Pain Management here.



One critical point is that the tests cannot differentiate between parent drugs and metabolites. For example, the opiate panel in a POCT test would be positive if any of the following drugs were present in the system: morphine, codeine, hydrocodone (Vicodin, Lorcet, Lortab), hydromorphone (Dilaudid) and heroin. Additionally, because drug levels must be greater than detection cut offs, false negatives remain a persistent problem.

Desktop or Tabletop Analyzer: This device measures a broader range of drugs and drug classes, including alcohol. Utilizes chromatographic technology. Physicians will need a specific license and trained staff to operate this equipment in their office. Although, more specific than a POCT cup this type of technology is still considered an initial screen. Most desktop analyzers with drugs of abuse screening are considered moderately complex by CLIA. Here's a helpful overview of screening vs. confirmatory testing.


Confirmatory Testing 


LC-MS/MS: Liquid chromatography, mass spectrum/mass spectrum liquid chromatography tandem mass spectrometry (LC-MS/MS) is a confirmatory technique that allows a laboratory to confidently identify and quantify a range of compounds. Unlike POC urine cups or immunoassay screening techniques, the LC-MS/MS allows for determination of a specific compound within a drug class. The available testing menu associated with LC-MS/MS is potentially extensive and includes synthetic opioids, controlled substances and drugs of abuse. This type of testing provides a numeric result. It is considered the “gold standard” of toxicology confirmatory testing.

GC-MS/MS: GC/MS is the abbreviation for gas chromatography/mass spectrometry, this testing methodology confirms presumptive positive drug screen specimens. GC/MS provides identification of the molecule(s) based on characteristic fragmentation patterns at specific retention times. GC/MS is a tandem technology, utilizing a gas chromatograph coupled to a mass spectrometer.


Cross Reactivity

Cross Reactivity can occur when structurally similar interfering compounds produce false-positive results on an immunoassay test (helpful chart here). For this reason, all positive results from rapid drug test devices are presumptive and recommendations often state they should be confirmed by a laboratory using an alternative methodology.


Opiate vs. Opioid


Hannah Freeman concisely summarizes the opiate vs opioid topic stating, “While subtle, the distinction between opioids and opiates is significant. An opiate is a drug naturally derived from the flowering opium poppy plant. Examples of opiates include heroin, morphine and codeine.

On the other hand, the term opioid is a broader term that includes opiates and refers to any substance, natural or synthetic, that binds to the brain’s opioid receptors – the parts of the brain responsible for controlling pain, reward and addictive behaviors. Some examples of synthetic opioids include the prescription painkillers hydrocodone (Vicodin) and oxycodone (OxyContin), as well as fentanyl and methadone. It is important to note that while all opiates are opioids, not all opioids are opiates."

Opiate: Opiates are a group of drugs that manage pain by depressing the central nervous system (CNS). There are two different kinds of opiates: natural and synthetic. Natural opiates come from the dried “milk” of the poppy plant and include opium, morphine and codeine. Heroin, for example, is made from the sap-like opium of poppy plants. Once cultivated, the opium resin is refined to make morphine, then transformed into different forms of heroin. Synthetic opiates, are man-made in a laboratory and are most often used to treat chronic or severe pain. Examples of synthetic opiates include Dilaudid, Demerol, Oxycodone, Vicodin, Fentanyl and Methadone.

Opioid: Opioids are a class of drugs that include illegal drugs like heroin, synthetic opioids such as fentanyl, and pain relievers available by prescription: oxycodone (OxyContin®), hydrocodone (Vicodin®), codeine and morphine among others. All opioids are chemically related and interact with opioid receptors on nerve cells in the body and brain.


Cheating the System

Whizanator: Tool utilized to hold synthetic urine in an undetectable fashion by patients trying to cheat on a urine drug test. Learn more here.

Synthetic Urine: Synthetic urine is a derivative fluid, designed to be similar to human urine. It is widely available on the internet (even on Amazon) and is commonly used by drug users to cheat urinary drug tests. Synthetic urine is utilized in the clinical laboratory field, primarily for laboratory calibration of screening equipment needed for urine testing.



Federal Five: The Department of Transportation (DOT) 5 panel drug screen is a screen for five classes of drugs. The test is mandated by the Department of Transportation to be given to employees of commercial driving companies. It has also been called the NIDA 5 for the National Institute on Drug Abuse and the SAMHSA 5 for the Substance Abuse and Mental Health Services Administration

The panel contains:

  • Amphetamines (speed, meth, crank, ecstasy)
  • Cannabinoids (marijuana, hash)
  • Cocaine (coke, crack)
  • Opiates (heroin, morphine, opium, codeine)
  • Phencyclidine (PCP)



Urine drug testing can play a critical role in monitoring patients receiving opioid therapy. It is not without controversy and has been an issue of increasing focus in the both the national news and in industry specific news outlets. It remains, however, a necessary component of regulatory compliance for opioid prescribers and helps to improve patient protocol adherence and safety. 

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