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Opiate Interpretation for Pain Medicine

Opioids are a large class of medications commonly used to relieve acute and chronic pain or help manage opioid abuse and dependence. Medications that fall into this class include: buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, tapentadol, tramadol, and others. 

Type of Opioids

  • Natural opioids (opiates)
    • Morphine
    • Codeine
    • Thebaine
  • Semisynthetic opioids
    • Heroin
    • Hydromorphone
    • Hydrocodone
  • Fully synthetic opioids
    • Methadone
    • Fentanyl
    • Tramadol
    • Pethidine
    • Levorphanol
    • Dextropropoxyphene
  • Opioid antagonists & agonist/antagonist
    • Buprenorphine
    • Naloxone

The American Society of Interventional Pain Physicians guideline states that urine drug testing must be implemented at initiation and during chronic pain management therapy. CDC issued new recommendations for prescribing opioid medications for chronic pain in March 2016 that include urine drug testing before starting opioid therapy and at least annually. The purpose of urine drug testing is to verify adherence to prescribed medications, identify undisclosed drugs, and discourage drug misuse, abuse, and diversion.

Opioids are readily absorbed from the gastrointestinal tract, nasal mucosa, lungs, and after subcutaneous or intermuscular injection. Opioids are primarily excreted from the kidney in both free and conjugated forms. The detection window for most opioids in urine is approximately 1 to 3 days with longer detection times for some compounds such as methadone.

Opiate immunoassays usually test for morphine, morphine-3-glucuronide, and codeine in human urine and gives a positive result if any of these opiates are present. They can also detects synthetic opiates related to morphine, such as hydromorphone, and high concentrations of the analgesic meperidine and the narcotic antagonist nalorphine. In general, opiate immunoassays do not reliably detect oxycodone, oxymorphone, meperidine, and fentanyl. Positive results for specimens containing other compounds structurally unrelated to opiates have not been observed. Immunoassay opiate cutoff for pain medicine compliance is 300 ng/mL.

However, if immunoassay results are inconsistent with prescribed therapy, the patient’s urine sample should be further analyzed by gas chromatography mass spectrometry (GC/MS) or liquid chromatography tandem MS (LC/MS/MS).  One study have demonstrated that the expected opioid was detected in 55% of patients but missing in 10%, while illicit drugs were detected in 20% and an unexpected opioid was detected in 15%. Primary care physicians and pain medicine specialists often have difficulty interpreting urine drug screen results when results differ from prescribed therapy. The following table can help clinical laboratories answer their questions. 

Interpretation Guidelines

Drug Class  Brand Name Expected Metabolites Noncompliant results Comments

Detection Window

Oxycodone

Oxycontin Percocet Percodan

Roxicodone

Endocet

Oxycodone 

Oxymorphone

Negative or any metabolites not listed   Oxycodone & oxymorphone detected. Hydrocodone is a pharmaceutical contaminant of oxycodone and may be present. 1– 3 days
Hydrocodone

Lortab, 

Lorcet

 Vicodan Hycodan Tussionex

Norco

Hydrocodone

Hydromorphone

Dihydrocodeine

Negative or any metabolites not listed  Hydrocodone is metabolized to hydrodromorphone & dihydrocodeine 1 –3 days
Hydromorphone

Dilaudid

Exalgo

Hydromorphone

Hydromorphone-3-glucuronide

Negative or any metabolites not listed   1-3 days
Oxymorphone

Numorphan

Opana

Oxymorphone

Oxymorphone-3-glucuronide

6-hydroxy-oxymorphone

Negative or any metabolites not listed    

Codeine

Tylenol #3

Codeine

Codeine-6-beta-glucuronide

Norcodeine

Morphine

Normorphine

Morphine 6 glucuronide

Hydrocodone

Negative or any metabolites not listed Codeine is metabolized to morphine so both may be present 1 –3 days
Methadone

Dolophine

Methadose

Amidone

Methadone

EDPP

 EMDP

Methadone only without metabolite, Negative or any metabolites not listed  Patients occasionally pour liquid methadone into their urine in order to test positive.  However, the methadone metabolite will be absent. 2- 3 days
Morphine

MS Contin

Duramorph

Avinza

Kadian

Morphine,

 normorphine,

 morphine 6 glucuronide

hydromorphone

Negative or any metabolites not listed  Detection of morphine can be due to morphine use, heroin use, or poppy seed consumption.  MS Contin patients usually develop very high urine morphine levels. Codeine is a pharmaceutical contaminant of morphine. 2 –3 days

Heroin

Does not apply

Heroin

Morphine

Morphine-6-glucuronide

Normorphine

6-Monoacetylmorphine

 6-acetyl- morphine is diagnostic for heroin abuse Heroin may be contaminated with acetylcodeine so codeine may be detected. Only morphine may be detected after 8 hours 12–24 hours
Fentanyl

Duragesic

Fentora

Sublimaze

Actiq

Fentanyl

Norfentanyl

Despropfentanyl

Negative or any metabolites not listed  Special GC/MS test is required for detection 1-2 days
Propoxyphene

Darvon

Darvocet

Propoxyphene

Norpropoxyphene

Negative or any metabolites not listed   2 days
Meperidine

Demerol

Mepergan

Pethidine

Meperidine

Normperidine

Negative or any metabolites not listed   2-3 days
Naloxone Narcan

Naloxone

Naloxone-3-beta-glucuronide

Negative or any metabolites not listed    
Buprenorphine

Buprenex

Suboxone

Norbuprenorphine

Norbuprenorphine glucuronide

Negative or any metabolites not listed    

 

References

Nagpal G, etal. Interpretation of Urine Drug Screens: Metabolites and Impurities. JAMA 2017;318:1704-5. 

Michna et al. Clin J Pain. 2007;23:173-9. 

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