Fentanyl is a synthetic mu-opioid agonist up to 100 times more potent than morphine and the dominant driver of US opioid overdose deaths.¹ It is most often sold as heroin or pressed into counterfeit pills, and is increasingly mixed with stimulants and non-opioid adulterants.² Novel analogues continue to emerge, and a fentanyl-negative result does not exclude an analogue.

US overdose deaths have fallen from a 2022 peak near 110,000; CDC provisional data estimate about 69,000 deaths for the 12 months ending January 2026, roughly a 13% year-over-year decline, attributed in part to reduced fentanyl purity and potency after 2022. Synthetic opioids, chiefly illicit fentanyl, still account for the majority of overdose deaths.³

Standard opiate immunoassays do not reliably detect fentanyl; a dedicated fentanyl/norfentanyl assay or LC-MS/MS is required. Definitive testing quantifies fentanyl and norfentanyl and reflexes to analogue panels when positive. Acetyl fentanyl and acetyl norfentanyl can appear as manufacturing impurities rather than metabolites.⁴ If fentanyl and norfentanyl are negative, analogues may not be tested unless specifically requested.

• Do not rely on a standard opiate immunoassay to detect fentanyl; order a specific fentanyl and norfentanyl test.
• A fentanyl-negative result does not exclude an analogue or nitazene; request expanded confirmation when suspicion is high.
• Expect prolonged detection in chronic illicit users; interpret persistent positives in that context, not as fresh use.⁵
• Screen for co-exposure to xylazine, medetomidine, and stimulants, which are not reversed by naloxone.
• Counsel that counterfeit pills and 'heroin' frequently contain fentanyl or analogues of unknown potency.