A UDT is only helpful if it accurately represents what drugs/medications a patient is consuming. While there are limits to testing even if the urine represents what the patient is actually consuming, unfortunately the situation can be further complicated if patients try to “cheat” the test (called “tampering”). This section covers what the most common methods are for tampering with a UDT, as well as some anti-tampering techniques your office may consider using to mitigate these risks..
A urine drug test is only as helpful as it is accurate. An inaccurate UDT however is not only unhelpful, but potentially very harmful if we put too much stock in the result.
While most of this manual has focused on what a result implies about the urine tested, we haven’t spent much time discussing whether that urine is truly representative of the urine that patient actually produced under physiological conditions. If a patient tampers with their urine then it may appear to not have drugs that it actually should, or have drugs present that were actually not consumed. Unfortunately, the potential for tampering introduces a whole new element into the challenges of UDT interpretation. Fortunately, it is uncommon. A report in 2015 suggested that 1.5% of the urine samples were adulterated by various means (this was not limited to just patients with pain however, and included patients receiving opioids for addiction treatment).1
Unexpected Negative Result
When we get an unexpected negative result by UDT it is easy to first come to the conclusion that the patient is either diverting their medication, not taking what they have been prescribed, or they are tampering with their sample. The following are what should be considered first when receiving unexpected negative results by UDT.
1) Detection Windows and Dose
It is possible to receive a negative result if you are testing the urine outside of the drug’s detection window for a particular assay. IA and GC/LC-MS have different detection windows for different drugs which can vary based on patient body mass or metabolic characteristics. If you perform a test too early or too late after ingestion of a drug you may receive a false negative. Also, lower doses of medication will have lower concentrations in the urine and may fall below the detection limits of the test, when compared to higher doses.
2) Metabolic Factors
Sometimes patients have extreme variations in their metabolic profiles. For example, some patients are deficient in cytochrome P450 and will produce low amounts of metabolites. Some patients use other medications that can inhibit metabolism such as through P450 pathways.
Drugs that typically require their own IA specific test
Acetaminophen
Amphetamines
Barbiturates
Buprenorphine
Benzodiazepines
Cocaine
Cotinine
Fentanyl
Ketamine
Ecstasy (MDMA)
Methamphetamine
Natural opiates
(codeine/morphine/heroin)
Methadone
Oxycodone
Phencyclidine
Propoxyphene
Tricyclic antidepressants
Marijuana
Tramadol
Synthetic Marijuana (K2)
Zolpidem
Methylphenidate
Alcohol
Lysergic Acid Diethylamide
Hydromorphone
Make sure you are using the right test for the metabolite you expect to measure. For example the opiate panel can detect oxycodone but only in high levels (opiate panel has low sensitivity for oxycodone). If you want to measure oxycodone compliance then you should use the oxycodone-specific IA panel which has a higher sensitivity. Also, you should wait until confirmatory testing with GC/LC-MS is completed to have increased confidence in a negative result.2–6
There are three main ways of “cheating” a urine drug test through tampering:
- Dilution
- Addition of adulterants/oxidants
- Urine substitution
Dilution
One of the most common types of deception with respect to UDT is dilution of the sample, accounting for up to 60% of sample tamperings.1,7 Dilution is usually as simple as adding tap water or toilet water to the sample while the patient is in the washroom in an attempt to lower the concentrations of substances in the urine sample. A way to detect sample dilution is to measure urine creatinine levels, temperature and the specific gravity. Normally urine creatinine is greater than 20 mg/dL so anything less than this becomes suspicious for dilution. Less than 5 mg/dL is inconsistent with human urine. Dilution via addition of water can also change the urine’s temperature to a level inconsistent with human urine. Temperature outside the normal of 32-38°C within 15 minutes of sample production is suspicious of tampering. A specific gravity less than 1.002 is also suspicious for dilution. Although creatinine levels and specific gravity can measure the dilution of urine, always keep in mind that these values can be low due to over hydration, diuretic use, low body mass or kidney diseases that cause renal tubular dysfunction.2-4,6
Addition of Adulterant or Oxidant
The addition of chemicals such as household cleaners, special chemicals designed to interfere with the drug assays by masking metabolites, or shavings of the drug being tested to produce a false positive, can all be ways patients may tamper with their urine samples. These account for about 28% of tamperings.1,7 There are several commercial adulterants and oxidants such as glutaraldehyde, sodium nitrite, potassium nitrite, pyridinium chlorochromate, peroxide and peroxidase. Common household adulterants include bleach, liquid drain cleaner, soap, ammonia, hydrogen peroxide, lemon juice, vinegar and eye drops. There are some adulterant and oxidant assays that are designed to detect some of these products in the urine. If you are not testing a urine sample specifically with adulterant assays you can detect tampering by visually inspecting the urine for its normal clear pale yellow colour or by observing long lasting bubbles after shaking which are caused by the addition of soap or other adulterants. The pH of the urine should be between 4.5 and 8.0 with values outside this range indicating suspicion for contamination. The specific gravity should be greater than 1.002 and less than 1.020. Values outside this range can be caused by sample contamination. Urinary nitrite levels should also be less than 500 ug/mL but can be elevated in the presence of added nitrites. They can also be elevated in urinary tract infections. Addition of anything to the urine may also change its temperature outside the normal of 32-38°C within 15 minutes of sample production.
| Drug | Metabolite | Percent of Times Metabolite Observed (%) |
|---|---|---|
| Methamphetamine | Amphetamine | 88 |
| Methadone | EDDP | 97 |
| Buprenorphin | Norbuprenorphine | 97 |
| Fentanyl | Norfentanyl | 98 |
| Hydrocodone | Hydromorphone | 69 |
| Oxycodone | Oxymorphone | 93 |
Table from Pesce et al. 2012
Tampering through addition of small amounts of a drug into the urine sample by the patient with the intent of producing an artificially positive UDT result is harder to prove and is usually an incidental finding on confirmatory testing. If a drug was added to urine manually by the patient it will usually be present in extremely high concentration and its metabolites will be absent. For example, according to the adjacent table, if buprenorphine or methadone is detected with LC-MS/MS then 97% of the time their metabolites should also be detected. If the parent drug is detected in high amounts without their metabolite, then consider whether the drug could have been added to the urine sample, or the time of ingestion of the drug was extremely recent, or the patient has some metabolic variations such as P450 deficiency or inhibition.2-4
Urine Substitution
Another form of tampering is through urine sample substitution. This accounts for approximately 14% of tampering cases.1,7 Patients may use someone else’s urine which does not contain any concerning substances, or contains the drug profile required to obtain an expected result during routine UDT. A good indicator of tampering by substitution is the temperature of the sample. The normal initial temperature of urine is 32-38°C. The temperature of the urine should be at least 32-33°C for 15 minutes after the production of the sample. If the urine is lower than this temperature it could be because of a time longer than 15 minutes since production of the sample or dilution of the urine with water or other liquid.2,3,6
Anti-tampering Strategies
It is worth noting that anti-tampering strategies fall along a spectrum that could be loosely broken down into being being cheaper and less invasive on one end of the spectrum, to more expensive and more invasive on the other end of the spectrum. Examples are included in the table below, from least invasive to most.
Note that our clinic has employed anti-tampering measures for over five years now, with over 1000 test results on chronic pain patients as well as patients with opioid use disorder and we have had only one potential case of tampering detected (sample was cold, in a patient prescribe OAT for addiction). Measures that we have used include urine dip for creatinine, pH and specific gravity; checking urine temperature; and blue water in the toilet. Naturally, we are considering discontinuing anti-tampering methods given the effort it takes however, one could argue that these methods still have utility in that they dissuade tampering.
It is helpful to be reminded that if there is a strong therapeutic relationship – with open discussion, compassion and understanding – the patient’s drive to deliberately deceive you should be minimized.
| Anti-tampering strategies |
|---|
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Cases
Case 1
Jane is a 56 year old female requesting oxycodone for her chronic pain and says she knows only oxycodone helps it. You ask about past or current illicit drug use but she denies any. You ask to obtain a baseline UDT before starting her on a long-term opioid regimen. She is reluctant at first but eventually agrees. She gives a urine sample for IA testing. The IA strip contains indicators for opiates, oxycodone, methadone, cocaine and amphetamines as well as tampering indicators for pH, creatinine and oxidants. Her UDT results come back all negative, the pH is in the correct range, the sample is negative for oxidants but her creatinine measures as extremely low. You ask Jane about any diuretic use or kidney problems and she denies either. You excuse yourself from the room for a moment with the urine sample to shake it and inspect it. It’s colour is consistent with normal urine and there is no excessive amount of bubble formation. You also measure the temperature of the sample to be 25°C, much lower than the physiological temperature of human urine and it has been about 10 minutes since Jane produced the sample.
You should be suspicious of dilution of the sample. Further testing of the urine can be done to accurately measure the level of creatinine and specific gravity to determine if it’s within the physiological range. A repeat urine sample should also be requested.
Chapter Pearls
- Tampering is uncommon but very concerning.
- The most common method of tampering is dilution (adding water to the sample, or drinking large amounts of water beforehand to naturally dilute the urine - so that the concentration of an illicit drug consumed gets below the detectability limit).
- In our clinical experience, our anti-tampering methods have only detected a single case of tampering over five years (sample was cold, and it was provided by a patient receiving OAT for addiction - not a HARMS Program patient with CNCP). It is reasonable to consider not employing any anti-tampering techniques.
REFERENCES:
- Mahajan G. Ch. 46: Urine Drug Testing in Pain Medicine. In: Essentials of Pain Medicine. Fourth edition. Elsevier; 2018:405-417.
- Moeller KE, Lee KC, Kissack JC. Urine drug screening: practical guide for clinicians. Mayo Clin Proc. 2008;83(1):66-76. doi:10.4065/83.1.66
- Moeller KE, Kissack JC, Atayee RS, Lee KC. Clinical Interpretation of Urine Drug Tests: What Clinicians Need to Know About Urine Drug Screens. Mayo Clin Proc. 2017;92(5):774-796. doi:10.1016/j.mayocp.2016.12.007
- Pesce A, West C, Egan City K, Strickland J. Interpretation of urine drug testing in pain patients. Pain Med Malden Mass. 2012;13(7):868-885. doi:10.1111/j.1526-4637.2012.01350.x
- Collen MR. Urine drug screens. J Pain Palliat Care Pharmacother. 2011;25(4):395. doi:10.3109/15360288.2011.606295
- National Opioid Use Guideline Group (NOUGG). Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain. 2010. http://nationalpaincentre.mcmaster.ca/opioid_2010/.
- Standridge JB, Adams SM, Zotos AP. Urine drug screening: a valuable office procedure. Am Fam Physician. 2010;81(5):635-640.
- Owen GT, Burton AW, Schade CM, Passik S. Urine drug testing: current recommendations and best practices. Pain Physician. 2012;15(3 Suppl):ES119-133.