Opioids

Diagnosis

Indications for Testing

Laboratory Testing

  • For drug testing strategies and methods, see ARUP's Pain Management site
  • Specimen types
    • Urine testing
      • Confirm and quantitate opioids
      • Commonly used for compliance testing and for identifying inappropriate drug use or exposure; the time during which a drug can be detected is drug-specific
      • For more information, refer to Drug Analytes Detected in Plasma and Urine
    • Serum/plasma testing 
      • Best specimen to correlate physiological signs and symptoms (eg, impairment, toxicity, therapeutic response) with drug use or drug concentration; also used when urine is unavailable
      • For most drugs, the time during which a drug can be detected is shorter than for urine
      • For more information, refer to Drug Analytes Detected in Plasma and Urine
    • Meconium/umbilical cord tissue
  • Note: Many opioid metabolites are available as independent drugs and may be identified by testing; ratios of parent to metabolite may help determine whether a patient used only the parent drug or more than one drug
    • Metabolic Pathways for Opioids

Monitoring

  • The interpretation of opioid drug testing is complicated because some prescription opioids are metabolized into other prescription opioids; additional opioid presence may be due to metabolism and not direct use
  • The following information assists in the correct interpretation of opioid drug abuse testing results
    • Possible explanations for drug(s) prescribed but not detected include the following
      • Non-compliance
      • Dilute urine, leading to drug concentrations that fall below analytical detection limits
      • Time lapse between last dose and specimen collection
      • Accelerated metabolism due to drug-to-drug interactions, altered expression of drug metabolizing enzymes, genetic variation, or poor drug absorption
    • Possible explanations for drug(s) detected but not prescribed include the following
      • Drug metabolism (see discussion below)
      • Lack of disclosure of other prescriptions from health care providers
      • Process impurity of the pharmaceutical product
      • Voluntary use of non-prescribed drug(s)
      • Incorrect prescription drug used
    • Possible explanations for unexpected drug concentrations include the following
      • Dosing less or more frequently than prescribed
      • Time lapse between last dose and specimen collection
      • Other variables as described above
  • Differentiation between production from metabolism or from direct use of an additional drug can sometimes be discerned by metabolic pathways
    • Two general categories of metabolism are major pathways and minor pathways; percentage ratios provided below are derived from an ARUP database review in 2006 that included 2,114 positive urine opioid test results
    • Major pathways
      • Morphine as a metabolite of codeine
        • When free morphine as a percent of free codeine in a urine specimen is <55%, morphine may have come from metabolism of codeine and not from separate use of morphine
        • The conversion of codeine to morphine is mediated by the cytochrome P450 isozyme 2D6 (CYP2D6), which is known to exhibit genetic variability and is vulnerable to drug-drug interactions
          • Genetic testing for CYP2D6 variants is available separately
      • Morphine and 6-monoacetylmorphine as a metabolite of heroin
        • Detection of 6-AM, along with morphine, is definitive evidence for the use of heroin; however, failure to detect 6-AM (which has a short half-life) with morphine present does not rule out the use of heroin 
        • Morphine can be derived from other sources such as poppy seeds, codeine metabolism, and morphine-containing medications
      • Hydromorphone or dihydrocodeine as a metabolite of hydrocodone
        • When free hydromorphone as a percent of hydrocodone in a urine specimen is <30%, the hydromorphone may have come from metabolism of hydrocodone and not from separate use of hydromorphone
        • The percentage of dihydrocodeine derived from metabolism of hydrocodone is not well characterized
      • Oxymorphone as a metabolite of oxycodone
        • The percentage of oxymorphone derived from metabolism of oxycodone is not well characterized
    • Minor pathways
      • Hydrocodone as a metabolite of codeine
        • When hydrocodone as a percent of free codeine in a urine specimen is <40%, hydrocodone may have come from metabolism of codeine and not from the separate use of hydrocodone
      • Hydromorphone as a metabolite of morphine
        • When free hydromorphone as a percent of free morphine is <25%, hydromorphone may have come from metabolism of morphine and not from separate use of hydromorphone

Clinical Background

Opiates and related pain medications (opioids), while effective analgesics, can produce dependency and severe withdrawal effects. In overdose, opioids may contribute to life-threatening respiratory and neurological depression. Compliance with use of prescribed opioids is monitored in pain management programs and in treatment/rehabilitation to detect possible diversion and assure abstinence from non-prescribed drugs.

Other clinical applications of opioids testing include the following

  • Evaluate patient compliance with drug therapy, particularly in chronic-pain patients
    • Recent studies suggest up to 75% of patients are not compliant with drug therapy
  • Evaluate abstinence for rehabilitation clinics 
  • Explain clinical signs and symptoms of intoxication 
  • Document abuse 
  • Identify neonates exposed to opioids in utero who may experience withdrawal symptoms or be at risk for either acute or chronic complications

Epidemiology 

  • Prevalence
    • More than 100 million prescriptions filled annually in the U.S.
    • Approximately one million Americans are opioid-dependant
  • Sex – M>F

Risk Factors

  • Groups at particular risk – chronic pain management patients, health care providers, and those with a history of substance abuse or addiction
    • Screener and Opioid Assessment for Patients with Pain ( SOAPP®) is a widely used risk-assessment tool
  • Substance abuse often involves more than just opioids
  • Addiction is related to environmental factors; however, genetics may also contribute

Pathophysiology

  • All opioids are capable of producing tolerance and withdrawal
    • Tolerance is defined as a state of progressively decreased responsiveness to a drug
    • Withdrawal is defined as a constellation of symptoms that occur after a patient stops taking a drug
  • Opioids include many natural (opiate), synthetic and semi-synthetic forms that exert activity through an opioid receptor; the following drugs are discussed in this topic
    • Heroin (metabolites 6-monoacetylmorphine [6-AM] and morphine)
    • Morphine
    • Codeine
    • Hydrocodone
    • Hydromorphone
    • Oxycodone
    • Oxymorphone
  • Additional tests are available that detect opioid drugs not discussed in this topic
    • Buprenorphine
    • Methadone
    • Propoxyphene
    • Fentanyl 
    • Meperidine
    • Tramadol
    • Tapentadol

Clinical Presentation

  • Effects on organs
    • Central nervous system
      • Opiate euphoria
      • Withdrawal
    • Respiratory
      • Depression of respiratory drive
    • Gastrointestinal
      • Nausea
      • Emesis
      • Constipation

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Opiates, Screen Only, Urine 2005096
Method: Qualitative Enzyme Immunoassay

Confirm and quantitate opioids in urine

Detects morphine, hydrocodone, and similar compounds; for quantitation, see Opiates, Confirmation Only, Urine

For detection of oxycodone and/or oxymorphone, see Oxycodone/Oxymorphone Screen Only, Urine; for quantitation, see Oxycodone/Oxymorphone, Confirmation Only, Urine

    
Opiates, Confirmation Only, Urine 2005091
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Confirm and quantitate opioids in urine

Detects hydrocodone, free hydromorphone, free codeine, free morphine, and 6-acetylmorphine.

For detection of free oxycodone and free oxymorphone, see Oxycodone/Oxymorphone, Confirmation Only, Urine

    
Drugs of Abuse Confirmation/Quantitation - Opiates - Urine 0090364
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Confirm and quantitate opioids in serum or plasma

Drugs covered – codeine, dihydrocodeine, morphine, hydrocodone, hydromorphone, oxycodone, oxymorphone and 6-monoacetylmorphine (heroin metabolite)

  

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Drugs of Abuse Confirmation/Quantitation - Opiates - Serum or Plasma 0092354
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Confirm and quantitate opioids in serum or plasma

Drugs covered – codeine, dihydrocodeine, morphine, hydrocodone, hydromorphone, oxycodone, oxymorphone and 6-monoacetylmorphine (heroin metabolite)

For medical purposes only

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Opiates, Screen with Reflex to Confirmation, Urine 2005093
Method: Qualitative Enzyme Immunoassay/Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Confirm and quantitate opioids in urine

Detects morphine, hydrocodone and, similar compounds.

For detection of oxycodone and/or oxymorphone see Oxycodone/Oxymorphone Screen with Reflex to Confirmation, Urine

    
Oxycodone/Oxymorphone Screen Only, Urine 2005103
Method: Qualitative Enzyme Immunoassay

Confirm and quantitate opioids in urine

Detects oxycodone and/or oxymorphone; for quantitation, see Oxycodone/Oxymorphone, Confirmation Only, Urine

For detection of morphine, hydrocodone, and similar compounds, see Opiates, Screen Only, Urine; for quantitation see Opiates, Confirmation Only, Urine

    
Oxycodone/Oxymorphone, Confirmation Only, Urine 2005097
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Confirm and quantitate opioids in urine

Detects free oxycodone and free oxymorphone

For detection of hydrocodone, free hydromorphone, free codeine, free morphine, and/or 6-acetylmorphine, see Opiates, Confirmation Only, Urine

    
Oxycodone/Oxymorphone Screen with Reflex to Confirmation, Urine 2005100
Method: Qualitative Enzyme Immunoassay/Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Confirm and quantitate opioids in urine

Detects oxycodone and oxymorphone

For detection of morphine, hydrocodone, and similar compounds, see Opiates Screen with Reflex to Confirmation, Urine

    
Drugs of Abuse Confirmation/Quantitation - Opiates - Meconium 0092314
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Confirm and quantitate opioids in meconium

Drugs covered – codeine, morphine, hydrocodone, hydromorphone, oxycodone, oxymorphone and 6-acetylmorphine (heroin metabolite)

Only performed on infants in the first days of life when meconium is excreted

For medical purposes only

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Additional Tests Available
 
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Methadone and Metabolite - Confirmation/Quantitation - Urine 0090362
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Methadone and Metabolite - Confirmation/Quantitation - Serum or Plasma 0090699
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Drugs of Abuse Confirmation/Quantitation - Methadone & Metabolite - Meconium 0092313
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Drugs of Abuse Confirmation/Quantitation - Propoxyphene & Metabolite - Urine 0090368
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Drugs of Abuse Confirmation/Quantitation - Propoxyphene & Metabolite - Serum or Plasma 0091363
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Drugs of Abuse Confirmation/Quantitation - Propoxyphene & Metabolite - Meconium 0092524
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Fentanyl and Metabolite - Confirmation/Quantitation - Urine 0092570
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Fentanyl and Metabolite - Confirmation/Quantitation - Serum or Plasma 0092569
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Buprenorphine and Metabolites - Confirmation/Quantitation - Urine 2002749
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Buprenorphine and Metabolites - Confirmation/Quantitation - Serum/Plasma 2002742
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Meperidine and Metabolite - Confirmation/Quantitation - Serum or Plasma 2002756
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Meperidine and Metabolite - Confirmation/Quantitation - Urine 2002760
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Tramadol and Metabolites - Confirmation/Quantitation - Serum or Plasma 2002764
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Tramadol and Metabolites - Confirmation/Quantitation - Urine 2002736
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Tapentadol and Metabolite - Confirmation/Quantitation - Serum or Plasma 2003133
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Confirm and quantitate tapentadol and metabolite in serum or plasma

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Tapentadol and Metabolite - Confirmation/Quantitation - Urine 2003128
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Confirm and quantitate tapentadol and metabolite in urine

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Drug Screen, Targeted with Reflex to Confirmation, Serum or Plasma 2005444
Method: Qualitative Liquid Chromatography-Time of Flight Mass Spectrometry/Quantitative Gas Chromatography-Mass Spectrometry/Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Panel includes components on Drug Screen, Targeted (see below); all present results are reflexed to confirmation testing
Drug Screen, Targeted, Serum or Plasma 2003254
Method: Qualitative Liquid Chromatography-Time of Flight Mass Spectrometry
 Panel includes opioids (buprenorphine, codeine, dihydrocodeine, fentanyl, heroin, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, propoxyphene, tapentadol, tramadol), stimulants (amphetamine, cocaine, methamphetamine, MDMA [Ecstasy], MDEA [Eve], MDA),  sedative-hypnotics (alprazolam, amobarbital, butalbital, clonazepam, diazepam, flurazepam, lorazepam, midazolam, nordazepam, oxazepam, pentobarbital, phenobarbital, secobarbital, temazepam, triazolam), cannabinoids and phencyclidine (PCP)
Drugs of Abuse 5 Panel, Urine - Screen with Reflex to Confirmation/Quantitation 0092182
Method: Qualitative Enzyme Multiplied Immunoassay Technique/ Quantitative Gas Chromatography-Mass Spectrometry/Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test

If specimen screens positive, Confirmation/Quantitation by GC/MS and/or LC-MS/MS will be added to confirm result
Drugs of Abuse 5A Panel, Urine - Screen with Reflex to Confirmation/Quantitation 0092183
Method: Enzyme Immunoassay/Gas Chromatography-Flame Ionization Detection/Gas Chromatography-Mass Spectrometry/Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test

If specimen screens positive, Confirmation/Quantitation by GC/MS, GC/FID, and/or LC-MS/MS will be added to confirm result
Drugs of Abuse 7 Panel, Urine - Screen with Reflex to Confirmation/Quantitation 0092184
Method: Qualitative Enzyme Multiplied Immunoassay Technique/ Quantitative Gas Chromatography-Mass Spectrometry/Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test

If specimen screens positive, Confirmation/Quantitation by GC/MS and/or LC-MS/MS will be added to confirm result
Drugs of Abuse 7A Panel, Urine - Screen with Reflex to Confirmation/Quantitation 0092185
Method: Enzyme Immunoassay/Gas Chromatography-Flame Ionization Detection/Gas Chromatography-Mass Spectrometry/Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test

If specimen screens positive, Confirmation/Quantitation by GC/MS, GC/FID, and/or LC-MS/MS will be added to confirm result
Drugs of Abuse 9 Panel, Urine - Screen with Reflex to Confirmation/Quantitation 0092186
Method: Qualitative Enzyme Multiplied Immunoassay Technique/ Quantitative Gas Chromatography-Mass Spectrometry/Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test

If specimen screens positive, Confirmation/Quantitation by GC/MS and/or LC-MS/MS will be added to confirm result
Drugs of Abuse 9A Panel, Urine - Screen with Reflex to Confirmation/Quantitation 0092187
Method: Enzyme Immunoassay/Gas Chromatography-Flame Ionization Detection/Gas Chromatography-Mass Spectrometry/Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test

If specimen screens positive, Confirmation/Quantitation by GC/MS, GC/FID, and/or LC-MS/MS will be added to confirm result
Drugs of Abuse 9 Panel, Serum or Plasma - Screen with Reflex to Confirmation/Quantitation 0092420
Method: Qualitative Enzyme-Linked Immunosorbent Assay/ Quantitative Gas Chromatography-Mass Spectrometry/Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test
Drugs of Abuse Panel, Meconium - Screen with Reflex to Confirmation/Quantitation 0092516
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Quantitative Gas Chromatography-Mass Spectrometry/Quantitative Liquid Chromatography-Tandem Mass Spectrometry

If uncertain about interpretation, call the technical supervisor or medical director of the lab performing the test

If specimen screens positive, Confirmation/Quantitation by GC/MS and/or LC-MS/MS will be added to confirm result