Dr. Thompson’s Blog
How to Keep a New Cyanide Antidote From Spoiling
Erik Kristofer Anderson
If you leave an opened container of yogurt in your fridge, it can spoil. I learned this the hard way when I created an accidental biology experiment in my fridge. Meanwhile, a sealed container of yogurt in the fridge for the same amount of time was just fine. I even had some of it for breakfast this morning.
It turns out that cyanide antidotes are kind of like yogurt: they can spoil in the fridge if they're not sealed properly. There is a new candidate molecule for a cyanide antidote, but it has an unfortunate habit of degrading in the fridge when using a standard storage container. An experiment in 2017 by a collaborative team of researchers led by Dr. Ilona Petrikovics and Dr. David E. Thompson tried to address this.
Cyanide is a toxin that causes dizziness, headache and, in high doses, death. Cyanide antidotes work by helping the body's own defense mechanisms. The human body has a method for converting cyanide into less toxic thiocyanate. This depends on molecules that contribute sulfur, known as sulfur donors.
The body has a limited amount of these sulfur donors, and when it runs out, it can no longer defend against cyanide. Cyanide antidotes work by providing more sulfur donors. With a replenished supply of sulfur, the body can work its magic and process the remaining cyanide.
There are currently two FDA approved cyanide antidotes in the US, and they work well. So why do we need another? Because both of these need to be injected intravenously, and that takes trained experts and is slow. Normally this wouldn't be an issue, but if a lot of people get cyanide poisoning at once, there would be a shortage of these experts.
Called a mass casualty situation, this could occur during an industrial accident or terrorist attack. To be better prepared for such a situation, we need to have a cyanide antidote that is easier to administer.
This new cyanide candidate I mentioned fits the bill. It is called dimethyl trisulfide (DMTS). My editor tells me that every time I use a new acronym I will lose half of my audience, so I will only use the one. DMTS can be injected in muscle, which is easier, faster, and requires less training than intravenous injection. Muscles are a bigger target than delicate veins.
The problem with DMTS is that it degrades over time when stored in the fridge. The researchers tested a new storage method to determine whether DMTS stored in this way kept its concentration.
DMTS can't be stored in water because it is barely soluble in water. Instead, it has to be dissolved in a solution of 15% polysorbate 80 in water. Polysorbate 80 is a molecule that works as a surfactant and emulsifier. This means that, among other things, it helps dissolve some things in water that wouldn't otherwise dissolve. Polysorbate is also used in food and cosmetics and is FDA approved for use in humans.
In previous experiments, a solution of DMTS in water with 15% polysorbate 80 lost concentration over time in a fridge. The container had a double seal: the first was a snap top on a vial, then the second was a crimped septum on another vial. A crimped septum is a metal cap with a rubber membrane. The metal cap gets crimped, or squeezed, onto the lid of the container.
The precise mechanism for DMTS concentration loss wasn't determined but two possibilities include DMTS evaporating or DMTS reacting with molecules from the air. It is significant that both of these mechanisms assume exposure to air.
To investigate this, the scientists designed an experiment to test whether completely sealing the DMTS solution off from the air would protect it from losing concentration. The question was: will DMTS in a fire-sealed glass ampule maintain its concentration?
A glass ampule is a type of glass bottle and once it has been sealed by fire it is hermetically sealed, meaning that it is completely airtight. Fire-sealing works by having an ampule with a narrow opening, using a flame to soften the glass, then pressing the glass around the opening to create a seal.
The researchers put two types of samples in the fridge: DMTS in the fire-sealed ampules and DMTS in the vials with a snap cap and a crimped septum. At certain times over the course of 100 days, three samples of each type were put through a high performance liquid chromatography machine (I would use an acronym here, but I promised not to). This is a method to separate chemicals and measure their concentration.
As expected, the snap cap and crimped seal samples showed a loss of DMTS over time. And, as hoped, the DMTS in the fire-sealed ampules showed no loss over 100 days.
In conclusion, the experiment showed that there is a way to store DMTS so that it won't degrade and lose concentration. This result makes DMTS continue to look like a good candidate for a new cyanide antidote that would help in case many people get poisoned by cyanide at once.
Erik Kristofer Anderson is a freelance science writer from Chicago. He holds a Master of Science in Chemistry from the University of California Berkeley, where he studied photosynthesis using ultrafast laser spectroscopy. In 2007, he worked as an undergraduate resesarcher in Dr. Thompson’s lab at Lawrence University. His interests include renewable energy and sustainability. He can be found at www.erikand.com.
Kiss, Lóránd, et al. "Sealing effects on the storage stability of the cyanide antidotal candidate, dimethyl trisulfide." Drugs in R&D 18.1 (2018): 45-49. (link)