Repurifying Radiochemicals for Testing
When radiochemicals degrade, they need to be cleaned up
Travel can be a draining process for radiochemicals. Much like people, they can arrive at their destination feeling not so fresh. When the radiochemical in question is in transit from a pharmaceutical, agrochemical, or animal health company to a testing facility for a program with a tight timeline, that can pose a big problem.
For a study using a radiochemical test item to be robust, the chemical must be at least 95% radiopure but preferably higher than 97%. If a test item is not radiopure, then two things can occur. Firstly, researchers might see unwanted side effects and reduced potency in synthetic impurities or degradation products that would not occur with the pure radiochemical. Secondly, impurities and degradation products may have similar structures to the compound being tested. This can make it challenging to discern results achieved from the test item against those resulting from undesirable impurities and degradants. For example, there may be no way to know which metabolites have come from the test item versus other compounds present in the radiochemical dosing solution after this is applied to a test system.
Take for example radiolabeled testing of agrochemicals. Before a new plant protection product can be approved for use, researchers must determine its environmental fate and metabolism. If it is sprayed on the surface of the plant, applied to a soil, or administered to an animal how does the test item and its subsequent metabolites disperse within the test system and how much of each is present? What metabolites are formed? Are these of toxicological concern? Aside from environmental risk considerations, it is also important to consider the impact on edible commodities such as fruit, dairy products and meat so dietary risk can be evaluated.
To find out, researchers typically use radiolabeled versions of their test item so they can easily trace where it travels and determine its eventual fate. A radioactive isotope, such as carbon-14, is added to the test chemical, either through isotope exchange reactions (replacing a stable atom in the test chemical with a radioactive isotope) or by attaching the radiolabel to the compound through a chemical bond. After the radiolabeled test item has been applied to the test system (e.g. a plant), the radiolabel provides a fingerprint to follow and the distribution of the radiochemical can be tracked.
Typically, a synthetic chemistry laboratory acting on behalf of a client will produce a batch of the radiochemical to be sent to a company like Charles River for testing. This is the stage where the chemical is at the mercy of shipping. This past year especially, between COVID-19 shipping delays and the confusion surrounding Brexit, the radiochemical could spend long periods sitting in storage before reaching its destination. Despite best practice around sample storage (e.g. using dry ice and storing sensitive chemicals under argon and protected from light), it might need repurification if it is found to be impure upon receipt at the testing facility.
Test facilities like Charles River Edinburgh can test and repurify the chemical when it arrives and take it straight from the lab to the testing site on the same campus. Chemicals that have degraded to as little as 20% radiopurity have been repurified and recertified using chromatographic means, ready for application to the test system. The only other option is to have the client send the test item again, where it could become subject to the same shipping delays as the original batch.
Repurification services allow testing facilities to bring the radiochemical up to snuff. When the repurification and the testing occur on the same campus, researchers can ensure that the freshest, highest purity chemicals are used for crucial safety and environmental fate studies, thus improving the accuracy of the data.
Charles River Associate Director of Chemistry, James O'Neill, MChem, PhD contributed to this article.