Interpretation and Limitations of Opiate Urine Drug Tests

Posted by Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP on

Background

Urine drug tests are commonly sent for patients in the emergency department, however care should be taken when interpreting the results of these tests given their limitations. The American College of Medical Toxicology published a position statement on the interpretation of urine opiate and opioid tests [1]. In this publication, they outline many of the limitations of opioid urine drug tests and explain why they exist.

Evidence

  • Though often used interchangeably, the terms opiate and opioid are not the same. ‘Opioid’ is the broad category name while ‘opiate’ simply refers to the naturally occurring opioids. The term ‘opioid’ encompasses opiates (e.g., morphine, codeine, opium), semi-synthetic agents (eg, heroin, hydrocodone, hydromorphone, oxycodone), and synthetic agents (eg, methadone, fentanyl, tramadol). Notice the name of the urine drug test next time you order one, it is likely specific for opiates (not opioids). This is because many tests are designed to identify morphine, though they will also detect codeine and heroin as they are both ultimately metabolized to morphine.
  • The standard urine drug tests do not specifically look for oxycodone, hydrocodone, etc. However, they can trigger a positive result due to their structural similarities, but not in every case. Therefore, a negative result doesn’t rule out use of these common drugs.
  • Similarly, synthetic opioids will not reliably cross-react with the opiate urine drug test as they are quite structurally dissimilar. In order to detect some of these agents, a test specific for the compound in question should be used.
  • As there are numerous different manufacturers of urine drug tests, hospitals may not utilize the same tests. In order to further understand the methods and cross-reactivity of a hospital’s specific urine drug test, the hospital’s laboratory should be contacted to request the package insert. Below is an example of the cross reactivity between various opioids with a opiate urine drug test [2].
Cross-reactivity of Various Opioids with Morphine Urine Drug Test [2]
Compound Equivalent to 300 ng/mL Morphine (ng/mL) Cross-reactivity (%)
Codeine 224 134
Heroin 366 82
Hydrocodone 1,086 28
Hydromorphone 1,425 21
Oxycodone >75,000 <0.4
Meperidine >100,000 <0.3

Previous ALiEM posts discuss further limitations of urine drug tests, specifically for benzodiazepines and opiates.

Bottom Line

  • The term ‘opioid’ is the broad class of substances, while ‘opiate’ refers to the naturally occurring opioids (e.g., morphine, codeine)
  • Many urine drug tests are designed to identify morphine and will also detect codeine and heroin, as they are ultimately metabolized to morphine
  • Due to structural similarity, some semi-synthetic opioids may cross-react but fully synthetic opioids are unlikely to cross-react

Want to learn more about EM Pharmacology?

Read other articles in the EM Pharm Pearls Series and find previous pearls on the PharmERToxguy site.

References

  1. Stolbach A, Connors N, Nelson L, Kulig K. Acmt position statement: interpretation of urine opiate and opioid tests. J Med Toxicol. 2022;18(2):176-179. doi: 10.1007/s13181-021-00864-1. PMID: 34780053.
  2. Opiates II [package insert]. Indianapolis, IN: Roche Diagnostics; 2006.

Author information

Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP

Leadership Team, ALiEM
Creator and Lead Editor, Capsules and EM Pharm Pearls Series
Attending Pharmacist, EM and Toxicology, MGH
Associate Professor of EM, Division of Medical Toxicology, Harvard Medical School

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