New method could detect deadly designer drugs faster

By Stephen Beech

Deadly designer drugs could be more easily detected using a high-tech new method, say scientists.

Some new drugs replicate the effects of known illicit substances, but can't presently be identified in urine samples as there is no specific test for them.

Scientists say the chemical structure variations that help such compounds avoid detection also make them "unpredictable" once inside the body - posing serious health consequences.

Now, an American research team - including a high school student - has used computer modelling to create a database of predicted chemical structures for improved detection of potentially thousands of different designer narcotics.

Jason Liang, a student at Montgomery Blair High School, Maryland, said: “This library of computationally generated metabolic signatures and mass spectra, which we’re calling the Drugs of Abuse Metabolite Database or DAMD, could lead to more thorough detection of new psychoactive substances and more accurate surveillance of designer drug usage."

An illicit drug that can be misused is usually identified by its chemical “fingerprint,” called a mass spectrum.

That fingerprint is a pattern created by the shape, weight and makeup of the drug molecule.

When a person’s urine is screened for drugs, a technician uses a technique called mass spectrometry to acquire and compare spectra from molecules in the sample to catalogues of spectra for known drugs and their metabolites - small molecules created when the body breaks down a drug.

But new psychoactive substances and their metabolites don’t usually have matches in existing databases.

Computer whizz Liang’s mentor, Dr. Tytus Mak, a statistician and data scientist at the National Institute of Standards and Technology (NIST), Maryland, said: “It’s a bit of a chicken and the egg problem.

“How do you know what this new drug is if you’ve never measured it, and how do you measure it if you don’t know what you’re looking for?

"Using a computational prediction methodology could help us find a solution.”

The idea to develop DAMD started with Dr. Mak and Dr. Hani Habra, formerly of NIST and a current bioinformatician at Michigan State University.

They believed that computer modeling could keep up with the seemingly endless replications of unknown synthetic compounds burdening health care systems and challenging drug surveillance initiatives.

Then, in the summer of 2024, Dr. Mak and Dr. Habra approached Liang about working with them.

Liang said: “Building a predicted mass-spectral library requires strong programming skills and a solid foundation in chemistry - both of which align well with my background.

“After learning about the devastating number of overdose deaths, including cases within the local community, I was eager to work on this project that could potentially help people.”

The research team used the mass-spectral database maintained by the U.S. Drug Enforcement Administration-chaired Scientific Working Group for the Analysis of Seized Drugs (SWGDRUG).

That database provides reliable mass spectra for the identification of more than 2,000 drugs confiscated by law enforcement officers.

Then, using computational approaches, the team predicted nearly 20,000 chemical structures and corresponding mass-spectral fingerprints for possible metabolites of SWGDRUG substances and their metabolites.

The team is currently validating their predicted mass spectra by matching them to real spectra from datasets of human urine analyses.

The datasets are catalogues of spectra from all detectable substances found in human urine samples.

Dr. Habra says that finding a match, or something close to a match, in the datasets “tells us if the chemical structures and spectra our algorithms are producing are plausible.”

Subsequently, the team will compare already-collected, real-world data to DAMD, showing a proof-of-concept for forensic toxicology.

The team says DAMD could someday be a publicly available supplement to the current illicit drug mass-spectral databases, making it easier to detect and identify evidence of drug use in human urine samples.

One of its primary applications is to develop a system to help people get the medical interventions they need.

Dr. Mak added, “Someone could have ingested a substance that, unbeknownst to them, was cut with a fentanyl derivative.

“Using DAMD, a doctor could see metabolites from the person’s toxicological report that are strong candidates for a fentanyl-like drug and inform their treatment plan.”

Liang is due to present the team's findings at the fall meeting of the American Chemical Society (ACS) in Washington, DC.