Opioids

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morphine, oxycodone, oxymorphone, hydrocodone, hydromorphone, buprenorphine, methadone, meperidine, propoxyphene (withdrawn from the US market), nalbuphine, fentanyl, levorphanol, butorphanol, pentazocine, tapentadol, tramadol.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).