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Opioids


Definition


  • Opioids are natural and semisynthetic alkaloids prepared from opium and synthetic compounds whose pharmacologic properties, rather than structure, mimic morphine.
  • Specific names: heroin, codeine, morphine, oxycodone, oxymorphone, hydrocodone, hydromorphone, buprenorphine, methadone, meperidine, propoxyphene (withdrawn from the US market), nalbuphine, fentanyl, levorphanol, butorphanol, pentazocine, tapentadol, tramadol.
  • There is no single test that will screen for/confirm all the opioids listed.
  • Normal range: drug and use dependent.

Use


  • Treatment of pain, usually moderate to severe
  • Preoperative sedation
  • Postoperative analgesia and surgical and medical emergencies including myocardial infarction, trauma, burns, orthopedic pain
  • Management of chronic pain associated with cancer
  • Antitussive and antidiarrheal agent
  • Detoxification and maintenance therapy of opiate addicts

Limitations


  • Screening
    • Typically performed in urine
    • Immunoassay-based technology performed on automated chemistry analyzers
      • EIA (KIMS, CEDIA), EMIT, RIA, FPIA
      • Qualitative
      • Target: morphine, morphine " “glucuronide
        • These "opiate " ¯ assays do not detect the semi/synthetic opioids, which include buprenorphine, methadone, meperidine, propoxyphene, nalbuphine, fentanyl, levorphanol, butorphanol, pentazocine, tapentadol, and tramadol.
        • These "opiate " ¯ assays have variable cross-reactivity with oxycodone, oxymorphone, hydrocodone, and hydromorphone.
        • Cutoff concentration " ”user defined.
          • 300 ng/mL
          • 2,000 ng/mL
    • Specific immunoassays are available for individual synthetic compounds.
      • Oxycodone: cutoff concentration 100 ng/mL; depending on the manufacturer, may exhibit approximately 100% cross-reactivity with oxymorphone
      • Methadone: cutoff concentration 300 ng/mL; depending on the manufacturer, may exhibit approximately 40% cross-reactivity with methadol
      • Buprenorphine: cutoff concentration 5 ng/mL; typically do not exhibit cross-reactivity with norbuprenorphine
      • Propoxyphene: cutoff concentration 300 ng/mL; depending on the manufacturer, may exhibit approximately 60% cross-reactivity with norpropoxyphene
      • Variable cross-reactivity with opioid metabolites
    • Several vendors offer assays in semiquantitative mode.
    • Immunoassay available specifically for heroin metabolite-6-acetylmorphine: cutoff concentration 10 ng/mL; <1% cross reactivity with morphine, codeine, and synthetic opioids
  • Screening in blood, serum
    • Immunoassay-based technology (FPIA, ELISA, RIA)
    • Opioid specific except for general "opiates, " ¯ which targets morphine with a cutoff concentration typically of 10 ng/mL
    • Target (cutoff concentration)
      • Fentanyl <1 ng/mL
      • Methadone 10 " “50 ng/mL; <5% cross-reactivity with methadol
      • Oxycodone 10 " “50 ng/mL; >50% cross-reactivity with oxymorphone
      • d-Propoxyphene 10 " “50 ng/mL; >400% cross-reactivity with norpropoxyphene
  • Confirmation/quantitation in serum, urine
    • Confirmation of urine samples often includes hydrolysis to cleave the glucuronide bond. In this case, the concentration provided is total drug (compared with free or unbound drug).
    • Common opioid confirmation profiles will include 6-acetylmorphine, morphine, codeine, oxycodone, oxymorphone, hydrocodone, and hydromorphone with limit of quantitation drug dependent but ranging 5 " “25 ng/mL.
    • Most synthetic opioids require individual specific tests for confirmation and quantitation; for potent low-dose synthetic opioids such as buprenorphine and fentanyl, the limit of quantitation is ≤1 ng/mL.
    • Sample preparation required: liquid " “liquid or solid-phase extraction.
    • Testing methodologies: gas chromatography, HPLC, GC/MS, LC/MSn (multiple Sn).
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