Sandia LabNews

Common ‘core’: Using molecular fragments to detect deadly opioids


Sandia detection method might someday be incorporated into hand-held instruments

Lethal amount of fentanyl next to a penny
JUST A BIT — A photo illustrating 2 milligrams of fentanyl, a lethal dose for most people, compared to a penny. Matthew Moorman, a Sandia researcher, has developed a new method to detect tiny amounts of fentanyl analogs based on their common molecular structures. (Image courtesy DEA)

Researchers at Sandia have developed a method to detect trace amounts of synthetic opioids. They plan to combine their approach with miniaturized sensors to create a hand-portable instrument easily used by law enforcement agents for efficient detection in the field.

Fentanyl is a fast-acting, opioid-based pain reliever that is 80 to100 times more potent than morphine. Illegally produced fentanyl often is mixed with other drugs such as cocaine or heroin and minuscule amounts can cause death by overdose. Drug overdose deaths have accelerated during the COVID-19 pandemic, according to the Centers for Disease Control and Prevention.

The chemical structure of fentanyl can be modified to create molecular analogs. These analogs can have different potencies, and the libraries of molecular “fingerprints” that current detectors require must be updated frequently to keep up with emerging analogs.

Matthew Moorman, a Sandia researcher, wanted to develop a method to detect fentanyl analogs based on their common molecular structures or “cores,” rather than by identifying the individual chemical decorations found on each one.

“A lower false-alarm rate with this detection method could lead to more efficient screening of trace amounts of opioids at the border or in mail-sorting stations,” he said.

There are thousands of possible analogs of fentanyl, says the Department of Homeland Security. Lab-based chemical analysis using sensitive techniques, such as infrared spectroscopy or mass spectrometry, can identify new analogs of fentanyl by their molecular fingerprints.

But the large number of possible fingerprints increases the possibility of false alarms from similar parts of a benign molecule. The result is that law enforcement agents may spend significant extra time doing secondary screening when their sensors did not detect an actual synthetic opioid. 

Detecting brand-new analogs

chemical structure of fentanyl
ALL IN THE FAMILY — The chemical structure of fentanyl (top right) and some fentanyl analogs with different chemical decorations. By decomposing fentanyl analogs, Matthew Moorman’s method allows for the detection the common molecular cores. (Courtesy of Wikimedia Commons)

To detect fentanyl analogs based on their common cores, Matthew and his colleagues used a technique that decomposed the molecular structure of several fentanyl analogs. They noticed that the process frequently produced the same molecular fragments.

Using a miniaturized ion-mobility spectrometer developed at Sandia for field-based explosives sensing, they could detect the synthetic opioid-based fragment in a less than a billionth of a gram of sample, even when mixed with agents that drug manufacturers commonly use to dilute the compounds.

Detecting a fragment common to fentanyl’s molecular core means this approach can detect analogs that law enforcement agents don’t know about yet, Matthew said. The small set of signatures also means the researchers could fine tune their chemical detection to create reliable, sensitive sensors.

The work to demonstrate the proof-of-concept fragment detection was funded by Sandia’s Laboratory Directed Research and Development program.

The researchers now want to combine this detection method with their miniaturized chemical sensors to develop an instrument that law enforcement agents could use in the field to detect the presence of synthetic opioids. They expect to have a functional, field-tested prototype within 3 years.

They also hope to apply the same fragment-based detection approach to other classes of illegal drugs, such as synthetic cannabinoids, cocaines and ketamines, Matthew said.