Pfizer's Paxlovid (1), possibly the drug that will bring down COVID, is not at all easy to synthesize. So much so that I wondered about the current (2) method used by Pfizer to make the stuff and whether the company will be able to manufacture enough to meet demand (assuming of course, that it receives EUA – pretty much a foregone conclusion).
For some background, a 2021 article in C&E News describes the superhuman effort required to make enough of the stuff to use for clinical trials [emphasis added]:
"The first 7 mg of the compound were synthesized in late July 2020. Encouraged by the early biological data, the Pfizer team aimed to scale up the synthesis. By late October, they’d made 100 g of the compound. Just two weeks later, the chemists had scaled up the synthesis to more than 1 kg. [Dafydd] Owen (3) said 210 researchers had worked on the project."
Bethany Halford, writing for C&E News, April, 2021
For those of you not familiar with organic synthesis or drug scale-up, what Halford described is no less than a superhuman effort. I'm astounded at what they pulled off, even with 20 plus years of pharmaceutical research under my belt.
While poking around, I came across something that I thought a bit strange. You can buy the stuff online, which made me wonder what kinds of chemicals/drugs can also be bought online. Here are three.
1. PF-07321332 (the active ingredient in Paxlovid)
MedChem Express, "The Master of Small Molecules," a company that may make fine chemicals but is clearly not "The Master of Modesty" will sell you PF-07321332. However, if you think that you're going to get the jump on the FDA and buy the drug before it's approved, think again. Here's one problem:
Here's another:
Purity 98.04%
I don't know what else is in there, but the maximum level of permitted impurities in drugs is usually less than 0.10%.
In case you're not yet dissuaded, it's a bit pricey:
According to Pfizer, when authorized, PF-07321332 will be given in a dose of 300 mg per day for five days. Let's screw up do some math! At the "discounted" price of $5,800 for 100 mg, you're gonna drop 87 large for one course of impure drug – a quantity that "The Master of Small Molecules" probably doesn't even have on hand.
2. Carfentanil
I only looked up this evil entity because I just wrote about 3-methylfentanyl, one of the worst fentanyl analogs now circulating in the US. A lethal dose is the size of one-sixth of a grain of salt. Carfentanil, which is used as an elephant tranquilizer, is even worse by 2-3 fold. No way this bad boy is sold online, right?
Wrong. Cayman Chemical sells it as a research reference sample dissolved in methanol. Here's a question to ponder: Since you now must show your driver's license to get a f###### box of Sudafed (and end up in a DEA database in the process), ordering this stuff goes on the "ACSH bad ideas of the week" list; right between taking medical advice from Joe Mercola and skydiving with a pina colada umbrella parachute. (4)
You want to get the DEA's attention? Ordering this will do the job quite nicely. Or, if you're a physician, write a prescription for one more Vicodin pill than Lord Andrew permits.
Lord Andrew was not pleased with the Vicodin.
3. Sarin
I was kidding around when I looked up Sarin, a mega-deadly (5) nerve gas that was developed by the Nazis during World War II. The stuff was so bad that Hitler was afraid to use it. Yet, I ran into this.
Perhaps World of Chemicals ("Connecting the World Chemically") should be renamed "World of Maniacs," since they not only will sell you Sarin but also ask how you want it packaged and delivered. Exceptional service indeed!
I would advise against it, but if you choose to order Sarin online you'd better have some damn good reasons when the FBI, Homeland Security, Secret Service, ATF, and Federal Marshalls, come a-calling. Steve did not:
Steve's defense - that he wanted to wrap up pastrami - didn't cut it. Photo by Ron Lach from Pexels
So, here are three bad ideas which you are welcome to try, but I don't recommend it. If you do choose to order them online, please let me know (from your cell or hospital room) how that worked out. And if you get lucky, Amazon Prime may even drop it on your front step (6). But probably not in time for Christmas. Sarin supply chain issues.
NOTES:
(1) Paxlovid is a mixture of PF-07321332 (the active drug) plus ritonavir.
(2) There are different types of syntheses required throughout the drug development process. The chemists who discovered the drug may need to make only a few grams, perhaps less. Then it's handed off to the process chemists who improve and scale up the synthesis. They make kilos of drug for all testing.
(3) Dafydd Owen is the director of medicinal chemistry at Pfizer. He didn't fire me. That was someone else.
(4) Cayman Chemical is not a bunch of dope pushers. They sell legitimate reference samples for research purposes, for example, comparing receptor binding affinities of different fentanyl analogs.
(5) VX is also a nerve gas, which is many times more toxic than Sarin. I couldn't find any loonies selling that. Maybe you can.
(6) I may burn in hell for this but isn't there something slightly amusing about the image of a porch pirate opening a stolen box of Sarin?