The U.S. Centers for Disease Control and Prevention has released a summary on a cluster of 14 deaths in Rhode Island earlier this year attributed to “acetyl fentanyl,” an analog of the potent, short-lived opioid used in pain management and outpatient anesthesia. The report, “Notes from the Field: Acetyl Fentanyl Overdose Fatalities — Rhode Island, March–May 2013,” appears in the August 30, 2013 issue of Morbidity and Mortality Weekly Report (MMWR).
The first 10 deaths were reported in the Providence Journal on May 13, 2013, leading CDC officials to join the team in the investigation. A total of 14 deaths were identified. Samples from the decedents gave positive ELISA results for fentanyl but GC/MS revealed an analog that authorities are calling acetyl fentanyl. A CDC health advisory released in June briefly details the chromatographic pattern and mass spectra.
Cayman Chemical Company, who offers the reference material, also calls it acetyl fentanyl, but offers desmethyl fentanyl as an alternative. The IUPAC name is N-phenyl-N-[1-(2-phenylethyl)-4-piperidinyl]-acetamide; fentanyl has a propionamide instead of the acetamide.
A CBC news story described a late April series of drug busts in Montreal that included seizure of a compound they called desmethyl fentanyl. The current MMWR release also links to an alert from the Pennsylvania Department of Drug and Alcohol Problems that reports 50 acetyl fentanyl deaths in the state this year, through June 27th (PDF).
Most curious is that the compound has not been described before as a recreational drug. It’s not available as a prescription drug anywhere in the world and is only a minor side product (0.04%) found in prescription fentanyl (DOI: 10.1016/j.jpba.2010.04.004).
In a lengthy discussion on Twitter last night and this morning with Chemjobber, SeeArrOh, and others, I initially asked whether acetic anhydride could have been used to acetylate fentanyl, thinking — without looking at the structure — that it was truly acetylated. I found later that fentanyl is made from 4-anilino-N-phenethylpiperidine (ANPP) using either propionyl chloride or propionic anhydride. Hence, acetyl fentanyl could be made by reacting ANPP with either acetyl chloride or acetic anhydride (That’s the extent of my synthetic expertise, Dear Reader.).
The major problem with acetyl fentanyl — or fentanyl for that matter — is its high potency relative to natural opioids like morphine or the more potent synthetic, heroin. As a result, the CDC recommends that emergency rooms and other facilities providing substance misuse care services stock up on the opiate receptor antagonist naloxone in anticipation of an increase in overdoses across North America.
But it looks like we’re stuck with acetyl fentanyl as the name. Any thoughts?
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