‘Masked’ fentanyl escapes controls, new technique reveals it

Retested samples and intercepted ‘designer drugs’ not detected by conventional tests

This summer in various areas of the USA the spotlight was on a new form of ‘masked’ fentanyl, fluorofentanyl, also considered 5 times more potent than a normal dose and believed to be responsible for several overdose deaths. Like other ‘designer drugs’ – modified versions of existing psychoactive substances, mostly approved drugs, constructed to circumvent laws and controls – it eluded conventional testing. A team of researchers from the University of British Columbia and the British Columbia Provincial Toxicology Center have tried to tackle this problem and have developed a more effective way to find out what new designer drugs are circulating in the community. In a study published in ‘Analytical Chemistry’ they demonstrated that high-resolution mass spectrometry can be used to analyze large-scale urine samples and discover molecules of emerging substances that had been missed by previous conventional tests.

The approach can help on the public health and safety front, experts say, because by enabling the rapid identification of new substances it can save lives and guide timely clinical responses to drug emergencies. Like that of fentanyl and its ‘disguised’ versions, precisely. With the new testing method, the researchers were “able to detect a number of substances circulating in British Columbia that were not being picked up by existing tests. Whenever new drugs emerge locally, this is important information that doctors and officials of public health may have,” highlights Michael Skinnider, study leader and lead author who conducted the research at the University of British Columbia, assistant professor at Princeton University.

Designer drugs have proliferated in the illicit market over the past two decades, experts note. They tend to be modified versions of other molecules, with similar effects but just enough structural changes to circumvent drug laws. Some can poison or even kill those who use them. The local Toxicology Center has identified over 20 different substances of concern by monitoring them since 2020. The researchers used high-resolution mass spectrometry to reanalyze more than 12,000 urine samples collected in British Columbia from 2019 to 2022. The retrospective analysis highlighted new synthetic opioids, benzodiazepines and stimulants that had escaped identification during initial screening. One of these, fluorofentanyl, is a modified version of fentanyl that was absent in samples before mid-2022 and then increased during the final months of the study. This suggests, the authors reason, that it was introduced into the local drug supply quite suddenly. Some of the other drugs also had distinct peaks during the two-year study period.

Typically to confirm the presence of a drug in a sample, a lab must first know what it is looking for and obtain it in synthetic form. This becomes a ‘reference standard’ which is used to develop a repeatable laboratory test, which leaves no doubt about the presence of the substance. However, these reference standards can be difficult to acquire. Finding hundreds for substances that may or may not be present in a community is expensive and impractical, so labs make educated guesses about which ones to acquire.

The goal of the study was to find a better way to prioritize the acquisition of reference standards. And researchers have thought of a new approach that is based on the use of high-resolution mass spectrometry. A urine sample should be imagined, they explain, as a puzzle with all its pieces scattered in the form of molecules. Mass spectrometry can precisely determine the weight and shape of each piece of the puzzle, which helps researchers figure out which ones fit into combinations typical of illegal drugs. If a lab anywhere in the world has published data on new drug molecules found in its samples, a lab in British Columbia can compare that data to its own and determine which drugs are most likely present locally. It is not a definitive confirmation, but it is enough to point the laboratory towards the right reference standards for more in-depth testing.

Retrospective analysis of samples within the study showed that the strategy can work. “Regularly applying this process will allow us to respond much more quickly to the emergence of new substances and significantly reduce the time between the introduction of a drug into the community and our ability to rigorously test it,” he said. said Aaron Shapiro, senior author of the study. The toxicology center is implementing the new tool in its clinical urine drug and drug screening and hopes to apply it to other datasets in the future.