Now this is one that I wouldn't have seen coming. In hospital settings it's common to use patient-controlled analgesia (PCA) pumps for management of severe pain. These infuse a solution containing morphine together with nonopioid analgesics directly into a patient's intravenous connection, and allow them to deal with their own experience of pain and their own tolerance for it. This system actually tends to result in lower analgesic doses than would otherwise be administered and improves the patient experience in general.

But a couple of years ago questions were raised about one commonly used mixture. There have naturally been IV solution stability studies of the main analgesics used (morphine, hydromorphone, esketamine, and metamizole), but it turned out that the morphine/metamizole combination was not as stable in solution (an effect first noted in doctoral work in 2009). Hydromorphone/esktamine mixtures were completely stable at 22C and at 37C, but while a morphine/metamizole mix held up at 22C, it showed significant ongoing loss of both components at 37 degrees. 

This turns out to be due to the formation of a Mannich condensation adduct between metamizole and morphine (shown at right) which has been given the name "metamorphine". Metamizole itself can decompose to provide the formaldehyde needed. This new paper characterizes it thoroughly and looks into its pharmacology, and it turns out to still be a nanomolar ligand at the mu-opioid receptor. That's 8- to 10-fold weaker than morphine, but still very much in the pharmacological activity range (remember, morphine is the standard by which opioid agonists are judged!) This was unexpected, since that's a pretty large group to hang off the morphine backbone. But there are some changes on the metamizole - metamorphine seems to have lost all of metamizole's anti-inflammatory activity.

As long as PCA pumps are kept at room temperature, this shouldn't be a problem. But if they are too close to the patient's body, left on or near warm equipment, or exposed to sunlight, you could see some problems. Never assume without checking that your chemicals are going to do what they're supposed to or remain what they say they are on the label - particularly in solution!

Otter sits on a capybara