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Fentanyl is a synthetic opioid analgesic that is widely used in surgical operations. Because it is 50 to 100 times more potent than morphine, fentanyl is also used for pain management in patients who no longer respond to high doses of morphine or oxycodone. Fentanyl is available for medical use as an injectable solution or a 72-hour transdermal patch. As a prescription, fentanyl is available under the brand names Actiq, Duragesic, and Sublimaze.

People with substance use disorders can obtain fentanyl by diverting it from legitimate medical supplies, or by purchasing it illegally. Synthetic fentanyl is sold illegally as powders, pills, liquids, and nasal sprays. Street names for the drug include Apache, China Girl, Goodfellas, Great Bear, Poison, and Tango & Cash.

Fentanyl analogues, such as acetylfentanyl, furanylfentanyl, carfentanil, and U-47700, are illicit drugs that have chemical structures that are similar but not identical to fentanyl. Carfentanil is about 10,000 times stronger than morphine. Fentanyl analogues are not easily identified because they require specialized toxicology tests for detection.

Fentanyl and its analogs are commonly mixed with heroin, cocaine, and methamphetamine contributing to the exponential growth of drug-related overdose deaths. Fentanyl overdose can result in respiratory depression, hypotension, loss of consciousness, coma, and death.

Analysis of a sampling of 1 million unique patients’ urine drug screens, showed that positivity rates for fentanyl had increased by 1,850% among cocaine users and 798% among methamphetamine users between January 2013 and September 2018.

Fentanyl overdose may cause small, constricted pinpoint pupils; choking or gurgling; cold and/or clammy skin; loss of consciousness; and slow, weak, or absent breathing. CDC reported 71,238 deaths in 2021 due to fentanyl overdose.

The circulating half-life of fentanyl is 3 to 7 hours. Fentanyl is mainly metabolized in the liver by CYP3A4 and 3A5 isoenzymes and transformed by a N-dealkylation to norfentanyl, which has negligible pharmacological activity. Seventy five percent of fentanyl and its metabolites are excreted in urine and nine percent in feces. Fentanyl can be detected in urine for 24 to 72 hours and norfentanyl for 96 hours after last use.

Fentanyl is not detected by urine drug screens for opiates, but specific fentanyl immunoassays are available. The LZI Fentanyl assay is a homogeneous enzyme is based on competition between drug in the urine sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. Enzyme activity decreases upon binding to the antibody. If no fentanyl is present in the sample, fentanyl-labeled G6PDH conjugate is bound to antibody, and enzyme activity is inhibited. When drug is present in the sample, antibody binds to free drug and the unbound fentanyl-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at 340 nm. A cutoff of 5 ng/mL to distinguish a preliminary positive from a negative result.

The preferred specimen is fresh urine, but urine can be refrigerated for up to 4 weeks before testing.


Poklis A., Fentanyl: a review for clinical and analytical toxicologists. Clinical Toxicology, 33, 439–447 (1995).

Poklis J., Poklis A., Wolf C., Hathaway C., Arbefeville E., Chrostowski L., Devers K., Hair L., Mainland M., Merves M., and Pearson J., Journal of Analytical Toxicology, 40:703–708 (2016).

Gonzales, E., Ng, G., Pesce, A., West, C., West, R., Mikel, C., Latyshev, S., and P. Almazan. Stability of pain-related medications, metabolites, and illicit substances in urine. Clinica Chimica Acta 416:80–85 (2013).

LaRue, L. et al. Rate of fentanyl positivity among urine drug test results positive for cocaine or methamphetamine. JAMA Netw. Open 2, e192851 (2019).

Walter K, Fentanyl Overdose, JAMA Patient Page, published online December 2, 2022. doi:10.1001/jama.2022.22462

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