Does fentanyl penetrate the skin? A Long, Overdue, Hell Dreaded Chemistry Lesson


It’s always fun to catch the New York Times when it makes a chemistry mistake. It happens from time to time, especially when they write about chemistry. I just caught one, but this time it’s not their fault.

“What is really going on in these police fentanyl exposure videos?” is an important article written by Zachary Siegel for the Times Magazine. The article recounted the apparent contradiction between the responses of some police officers who had touched street fentanyl and the expected symptoms of a fentanyl overdose. The conclusion? The officers had panic attacks – something that not every Narcan in the world would touch.

Zachary Siegel for The Times Magazine, 7/13/22

Siegal also quoted from a 2019 article by the Times editorial board:

Opioids must enter the bloodstream to exert an effect, and even the most potent ones cannot penetrate the skin quickly enough or in sufficient quantity for this to occur.

Although it sounds simple enough, the science is not unanimous. There is no shortage of studies on this subject (Google skin penetration of fentanyl and you will get 328,000 results) and after a brief search I was able to definitely find that the #1 drug doesn’t penetrate the skin, #2 Is penetrate the skin, or #3 maybe or maybe not penetrate the skin.

This is where Siegal makes a rather weird chemistry mistake in his piece. [emphasis mine]:

“[A]Ryan Feldman, 33-year-old clinical toxicologist and emergency pharmacist, has co-published a case study of when he accidentally spilled a gigantic dose of pure liquid fentanyl about himself at work; he simply washed it off, with no adverse effects.

The problem? There is no “pure liquid fentanyl” that is unless you are taking pure fentanyl solid fentanyl – its normal state – and melting it, a process that involves heating the substance to a temperature of 190°F, slightly lower than boiling water (2). I can think of many reasons why you might want to avoid this, especially since if you pour, say, a few ounces of boiling pure liquid fentanyl onto your skin, not only will you have no more skin to penetrate , but also the amount of molten fentanyl that now, in the absence of a skin barrier, will absolutely be absorbed by fat, blood and rotting flesh will likely be something like a million times the lethal dose of the drug . A pretty bad chemistry mistake, but this one can’t be blamed on The Times; Siegel got the term from the article that The Times cited to prove his point:

Source: R. Feldman and B. Weston, Prehosp Disaster Med. 2022 Aug;37(4):550-552.: doi:10.1017/S1049023X22000905. Published online June 20, 2022.

The verdict

Going back to the paragraph above where three rather disparate conclusions were presented, I will choose the article by Feldman and Weston (#1). Why? The other two articles were based on lab models of skin cell penetration which are somewhat useful in predicting the relative ease of penetration of different chemicals, but tell you little about how much will actually enter the bloodstream. This is article #1, albeit a single case study, that should dispel the myth of the dangers of simply touching a counterfeit pill contaminated with fentanyl. Because if somebody was going to be poisoned skin contact with the drug it is the unfortunate one who had this occur [emphasis mine]:

This case details dermal exposure to a large dose of analytically confirmed pharmaceutical fentanyl (fentanyl citrate, 10 micrograms of fentanyl base per ml), on a large skin surface. In addition, exposure occurred at a site with skin barrier compromise, a factor that may increase the absorption of fentanyl. The patient underwent appropriate decontamination and underwent a brief medical evaluation with no clinical effects of opioid exposure observed.

(It should also be noted that the solutions are much more likely to penetrate the skin than the dry chemical.)

Rather than “liquid fentanyl,” the authors were of course referring to aqueous fentanyl – a Aqueous solution of fentanyl, which contained 10 micrograms of the drug dissolved in 1 ml of water. Let’s illustrate the difference.

(Left) Saline solution. (Right) Liquid salt. Uh. Images: Wikidoc, DuBois Chemical

Granted, this is a single case study, but it certainly tests the skin hypothesis, and then some. The volume of fentanyl solution that was spilled is not given, but as it covered large area of ​​skin I’m going to take a wild guess – four ounces (118ml). Now let’s screw up To make calculations.

118 ml of a 10 micrograms per ml solution will contain 1180 micrograms (1.18 mg) of the medicine. The lethal dose of fentanyl is estimated at approximately 2 milligrams with significant individual variability. And fentanyl pain patches (2) come in four doses, the highest dose patch designed to deliver 100 micrograms of medication per hour. Given that the spill victim was exposed to an amount of approximately half a lethal dose and 12 times that of the patch at the highest dose, but washed it off and walked away without incident, it odds are that little or no fentanyl got through the skin, even though this person had a “skin barrier compromise” (presumably a cut).

So while inhaling or ingesting the stuff can get you all sorts of trouble, a simple spill shouldn’t. But in chemistry, there are always exceptions. Which means it’s time for the long delay…

Irving and Steve return. We missed them very much.

Guess who’s back?! Our old friends (and the animators of TDCLFH®) Steve and Irving! Yes, they’ve been away for a while, but not without good reason. Steve had been dodging goiter surgery since the 14th century, but eventually the thing grew to the size of a Vedalia onion and he had to act. When Doctor. Oz’s “Magic Goiter Burner” didn’t work, he gave in and went under the knife, and was off his feet (assuming he had any) for a while. Irving, the more adventurous of the two and a sports enthusiast, drove to Texas to attend a minor league baseball game in which the Amarillo Sod Poodles hosted the Corpus Christi Hooks. But Amarillo was too hot so he went home.

Yes, Amarillo Sod Poodles exist. Here is their logo. Free image: Zack Casciato, Pinterest

As far as skin penetration is concerned, solvents are important.

1. Alcohol

Ethyl alcohol is one of many known chemicals that help transport chemicals through the skin. This is usually shown by dissolving the chemical in ethanol (or gels that contain it) and water and comparing the amount of chemical that passes through. Compared to water, ethanol will almost always be superior at helping chemicals pass through the skin. This includes fentanyl, although your chances of accidentally coming across an alcohol solution of fentanyl are pretty much nil.

But alcohol does not need to be applied to affect absorption! A study of drunk rats showed that alcohol in the rat’s skin allowed chemicals like herbicides, pesticides, and mosquito repellents to enter the bloodstream of “polluted” rats 2-5 times better than in rats. their abstinent counterparts over a 24-hour period. period. This led study author Rhonda M. Brand to conclude:

“Extra precautions should be taken when handling chemicals if you have been drinking, even if it was a day earlier.

Expert advice for everyone.

2. Acetone (nail polish remover)

Acetone is of particular interest to organic chemists because it is the solvent we use to clean dirty glassware. Over our careers, we’ve probably spilled several thousand gallons of this stuff all over us, along with all the chemicals it washes out of the bottles. A Taiwanese study showed that acetone improved the skin penetration of sucrose, progesterone, caffeine and hydrocortisone, which makes me wonder how an organic chemist achieves his 40th birthday. A spill of fentanyl in acetone would be very scary.

3. DMSO – Big Daddy

Dimethyl sulfoxide is the king of solvents. Almost all organic chemicals (containing carbon, with a few exceptions) immediately dissolve in the substance. And some inorganic chemicals (lacking carbon) will also yield to its regal solvating powers while disdainfully mocking other solvents like ether, chloroform, or benzene. And DMSO is known to transport chemicals through the skin.

The classic example here is potassium cyanide. While pouring an aqueous solution of sodium or potassium cyanide on your skin isn’t a great idea, it probably won’t kill you, at least right away. The same is not true for a cyanide/DMSO solution.

“Contact with the skin [of a water solution] is not as concerning as if the cyanide was mixed with DMSO.”

Anne Marie Helmenstine, Ph.D., writing for ThoughtCo

Needless to say, if the fentanyl exposure described in The Times Magazine involved a DMSO solution instead of a water solution, the conversation would be quite different.

Finally, DMSO itself when applied to the skin is not toxic. You may remember that in the 1980s DMSO was touted as a treatment for arthritis (it doesn’t work). Arthritis sufferers toppled over to no avail. ‘Cause I had a lab and I was such a good grandson didn’t want to be cut off from his will Once I distilled it and took a bottle to my grandmother. It did nothing for her aches and pains, however, she died 9 years later. Did I accidentally kill my grandmother? I doubt. There are over 400 products containing DMSO on Amazon. They are sold as “supplements” of course, even though the product is only FDA approved for painful bladder syndrome, something I don’t need to research to know I can easily live with my life without ever experiencing it.

Conclusion

Although deadly when inhaled or ingested, fentanyl, in solid or aqueous solution form, does not pose many risks. But it should already be obvious. When pain patients who have been cut off their medication go to the streets to buy oxycodone and instead receive a bunch of counterfeit M-30s fortified with fentanyl, they don’t die holding the pills in their hands, only after taking them.

REMARKS:

(1) The drug was actually fentanyl citrate, which is the citric acid salt of fentanyl, a base. Citrate is a common counterion (in this case an anion) found in medications because it is harmless. Other common base drug salts (salts are more soluble in water) are hydrochloride, fumarate, mesylate…many others.

(2) An illustration of the difficulty of transdermal drug delivery is the Durogesic fentanyl transdermal patch. The highest dose patch is designed to deliver 100 micrograms of fentanyl per hour for 72 hours, for a total of 7.2 mg of fentanyl. How much fentanyl does the patch actually contain? It’s 16.8mg, which means less than half of the drug is delivered through the skin from a specially designed patch.

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