Acetyl Fentanyl: Dangerous, Poorly-Named Street Drug

Acetyl fentanyl HCl, courtesy of Cayman Chemical Company. Click on the image to view the source page.

Acetyl fentanyl HCl, courtesy of Cayman Chemical Company. Click on the image to view the source page.

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?

Author: David Kroll

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2 Comments

  1. Hi David,

    This is somewhat of an aside to your post.

    In the original CDC Health Advisory of June 20, 2013 (“Recommendations for Laboratory Testing for Acetyl Fentanyl and Patient Evaluation and Treatment for Overdose with Synthetic Opioids” at http://emergency.cdc.gov/HAN/han00350.asp), the table refers to “Acetanilide” as a synonym for acetyl fentanyl.

    While acetyl fentanyl could be remotely regarded as a chemical derivative of acetanilide, the two compounds are by no means synonymous. Acetanilide has its own distinct history as a (toxic) analgesic which eventually led to the discovery of acetaminophen.

    I suspect the error may have been propagated from the RI site (http://www.ri.gov/press/view/19576). On this site, the statement, “…Acetanilide, n-1-Phenethyl-4-Piperidyl — also known as acetyl fentanyl…”, might indicate to the lay person that three possible names exist for the same compound (because of the comma after “Acetanilide”).

    While the knowledgeable scientist would recognize this error, I note that Acetanilide has in fact now been used by lay people to refer to Acetyl Fentanyl.

    Although I informed the contact individuals indicated on the CDC website about this error (on June 24), I note that the table on the website has yet to be revised.

    Terra Sigillata is an interesting site and I commend you for it!

    - Peter

    Peter W. Mullen, PhD, FCSFS
    KEMIC BIORESEARCH
    P.O. Box 878
    Kentville
    Nova Scotia, B4N 4H8
    Canada

  2. UPDATE:

    I note that the CDC health advisory (at http://emergency.cdc.gov/HAN/han00350.asp) was recently (last week?) revised so that the table no longer indicates that “Acetanilide” is a synonym for acetyl fentanyl. Curiously, however, the site bears no update or revision date – i.e. It still states “Page last reviewed: June 20, 2013″ and “Page last updated: June 20, 2013″!

    - Peter