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They are hard to detect. They are extremely powerful. And they come in many forms.

This makes synthetic drugs like fentanyl particularly dangerous and hard to control.

But scientists are developing new methods to detect and identify these drugs while ensuring the safety of law enforcement officers, first responders and forensic chemists.

Safe, Efficient, Reliable: New Science in the Fight Against Killer Drugs

NIST researchers give law enforcement and public health experts new tools to combat fentanyl and other synthetic drugs.

In the shadow of COVID-19, an older epidemic continues to rage. More than 81,000 people died of drug overdoses in the United States in the 12 months ending last May. That is the highest number ever recorded and a nearly 20% increase from the same period one year before. 

This spike in deaths is being driven by fentanyl, a synthetic opioid that mimics the effects of heroin but is up to 50 times more potent. A graph of the overdose statistics from the Centers for Disease Control and Prevention shows the line for fentanyl turning sharply up starting in 2014. It’s been rising steeply ever since.

A line graph showing annual U.S. drug overdose deaths by drug category, 1999 - 2019.
Drug overdose deaths in the United States by drug category. Based on data from the U.S. Centers for Disease Control and Prevention.
Credit: B. Hayes/NIST. Source: U.S. Centers for Disease Control and Prevention

Fentanyl kills so many people in part because it is cheap, potent and easy to manufacture. In addition, clandestine chemists can easily cook up new varieties, or analogues, of fentanyl by tweaking its molecular structure. Dealers often spike heroin, cocaine and other drugs with fentanyl and its analogues. Users may not know what they’re getting, and they can more easily overdose as a result. 

The high potency and changeability of fentanyl also present challenges to first responders, police and forensic chemists. 

First, it is hazardous. During laboratory or field analysis, for example, particles can become airborne and even a small amount, if accidentally inhaled, can be dangerous.

Second, it hides behind other drugs. Analyzing drug mixtures that contain small but deadly amounts of fentanyl is complicated and requires the ability to detect substances at very low levels.

Third, it can fly under the radar. Traditional laboratory methods are not designed to detect and identify new drug analogues. This can hinder law enforcement and delay the public health response to newly emerging substances.

Black background. Photo of a penny. Next to the penny is a tiny amount of a white powder.
Photo illustration of 2 milligrams of fentanyl, a lethal dose in most people.
Credit: U.S. Drug Enforcement Administration

Drug abuse has plagued public health for decades, but the unprecedented toll of recent years reflects a new reality. Today’s illicit drugs are more dangerous and harder to control than the drugs of decades past. 

“A new drug might appear, then three or six months later it’s gone, replaced by something new,” said NIST chemist and program manager Marcela Najarro. “It’s a totally different ballgame than 10 or 15 years ago.”

Limiting the harm from the opioid epidemic requires expertise from public health, social science, law enforcement and other domains. But one often overlooked need is expertise in the area of analytical chemistry.

As the nation’s chemical measurements laboratory, NIST is working on analytical methods to meet these challenges. Researchers with NIST’s Forensic Science Program are developing new tools that can speed up the public health response to newly emerging synthetic drugs. They are also improving existing technologies, developing new ones, and collaborating closely with law enforcement organizations and forensic labs to help them successfully implement solutions. Here is a rundown of what NIST is doing.

Part I:
The First Line of Defense

Most of the fentanyl used illegally in the United States originates in China. Stopping shipments of the drug before they enter the country is the first line of defense. 

Fentanyl and its analogues enter the U.S. along two main routes. Bulk shipments arrive via Mexico, smuggled across the border at vehicle crossings. Smaller parcels arrive from China directly by airmail and commercial delivery services.

Consider the air shipping method first. At John F. Kennedy International Airport, roughly 1 million packages arrive from overseas every day. This presents a classic needle-in-a-haystack problem, but one that is made even more daunting by the fact that fentanyl is so potent. This means it can be profitably shipped in small quantities that are easy to conceal. 

At postal inspection facilities, officers use chemical detectors, trained detection dogs and X-ray machines to find packages that might contain fentanyl. But each package has to be individually inspected — a huge, labor-intensive and potentially hazardous job.

NIST is developing technologies that can help identify suspicious packages efficiently, reliably and safely. One approach involves blasting packages with high-pressure jets of air, then directing the airflow to sensors that can detect traces of narcotics. If any traces are found, those packages can be separated for manual inspection.

NIST originally developed this method, called aerodynamic sampling, for high-throughput screening of airport luggage for explosives. But the same approach can be used to detect narcotics. In this video, NIST researcher Matt Staymates explains how he uses specialized video techniques to understand and improve aerodynamic sampling.

NIST mechanical engineer Matthew Staymates explains how he uses specialized video techniques to understand and improve aerodynamic sampling, a safe and efficient method for high-throughput screening of packages for fentanyl.

The challenge at the border is also immense. More than 6 million trucks and nearly 77 million personal vehicles entered the U.S. through ports of entry along the southern border in 2018. NIST researchers are also testing and improving existing technologies that can be deployed in that very different operational environment.

What NIST Is Doing

Stopping Fentanyl at the Border: Can Chemical Detectors Help?

NIST scientists test the effectiveness of chemical screening at points of entry.

K9 Chemistry: A Safer Way to Train Detection Dogs

Canine trainers may no longer need to handle or expose dogs to real explosives and narcotics.

Sniffing Like a Dog Can Improve Trace Detection of Explosives and Narcotics

This artificial dog nose that mimics the “active sniffing” of a dog can improve trace chemical detection up to sixteenfold.

Evaluation of a Lateral Flow Immunoassay for the Detection of the Synthetic Opioid Fentanyl

This study demonstrates that LFIs have the potential to be used by law enforcement for the detection of synthetic opioids.

Part II:
Safe Handling in the Field and in the Lab

Police, first responders and forensic chemists face a new hazard: unknown substances of unknown potency. A bag of powder might be cocaine, or it might be fentanyl. Or it might be something worse.

Some synthetic drugs can be extremely dangerous. A fentanyl analogue called carfentanil, for instance, can be 100 times more potent than fentanyl — 5,000 times more potent than heroin. Drugs like this can be dangerous or even deadly if a small amount is accidentally inhaled.

This video clip, produced using a technique called laser light sheet imaging, shows how particles can become airborne when seized drugs are handled for testing. NIST videos like this one are used to train first responders and forensic chemists on the hazards posed by highly potent drugs like fentanyl. Credit: M. Staymates/NIST

To test seized drugs using conventional methods, police in the field or chemists in the lab have to open suspicious packages and handle the contents directly. “But with novel drugs, you have to assume they’re dangerous, because you don’t know how potent they are,” said Amber Burns, manager of the Maryland State Police forensic chemistry lab. “The best strategy is to minimize exposure.”

NIST scientists are working closely with Burns and other forensic chemists to develop new ways to test drug evidence that minimize exposure. One research collaboration recently showed that labs can get a reliable initial identification of seized material by swiping the outside of a package. Because this method does not require opening the package or handling its contents directly, it minimizes the risk of accidental exposure.

“With this method, labs can quickly identify hazardous samples and separate them for special handling,” said NIST research chemist Ed Sisco. “That speeds up workflow in the lab without compromising on safety.”

Accuracy also cannot be compromised. Forensic results in the hands of police and prosecutors can have a major impact on peoples’ lives. For this reason, NIST is helping labs ensure not only that these new methods are safe and efficient, but that they produce reliable results.

The researchers have published detailed accounts of how they implemented and validated these new methods so that other labs can follow suit. This helps ensure that these solutions can be implemented across the country and at scale.

The key to the success of these research projects is collaboration. In addition to running the Maryland State Police forensic chemistry lab, Burns is a visiting researcher at NIST. Similarly, Sisco is a guest researcher at the Maryland State Police forensics lab. This exchange of expertise helps ensure that the solutions NIST presents are realistic and address the real-world, complex problems that crime labs face.

This video describes one of many collaborative research projects aimed at protecting police and crime lab chemists from accidental exposure.

Scientists describe a new way for police and forensic chemists to test seized drugs while minimizing the risk of accidental exposure to fentanyl, a super potent drug that can be dangerous if a small amount becomes airborne and is accidentally inhaled. Image of lethal doses of heroin and fentanyl by Bruce A. Taylor/NH State Police Forensic Lab.

What NIST Is Doing

New Drug-Identifying Tech That Could Reduce Accidental Exposure to Fentanyl Is Coming to Maryland

WJZ 13 CBS Baltimore reports on study conducted by NIST and the Maryland State Police crime lab.

In Glowing Colors: Seeing the Spread of Drug Particles in a Forensic Lab

Black-light videos from NIST will help crime labs manage an invisible risk.

New Protocol for Measuring Background Levels of Drugs in Crime Labs

If chemists want to detect small amounts of drugs like fentanyl, they may need to keep an eye on background levels.

NIST DART-MS Database Forensics Database

A technology called DART-MS can help labs identify seized drugs quickly and with minimal handling, which reduces the risk of accidental exposure. This database of drug compounds and their chemical signatures is freely available on the NIST website.

Standard for Sampling Seized Drugs Approved for OSAC Registry

The Organization of Scientific Area Committees for Forensic Science (OSAC) has approved the Standard Guide for Sampling Seized Drugs for Qualitative and Quantitative Analysis for inclusion on the OSAC Registry — a trusted repository of high-quality, science-based standards for forensic practice.

Part III:
Rapid Identification of New Substances

Fentanyl is not just a killer. It’s also a shape-shifter. Illicit chemists easily cook up new analogues, each with a slightly different molecular structure. These can be far more potent than the original. This makes them particularly deadly to users, who don’t always know what they are consuming.

The potential number of analogues is immense. This is what fentanyl and a few of its analogues look like:

Fentanyl and its core structure These images show the molecular structure of fentanyl and the core structure within it that is common to fentanyl and most fentanyl analogs. N N O Fentanyl This is the molecular structure of fentanyl. N N N N O O Fentanyl This shows the core structure of most fentanyls. To create a fentanyl analogue, chemists leave the core structure intact but change atoms or groups of atoms around the core. C 2 H 3 O 2 N N N N O O Carfentanil This is carfentanil, which looks like fentanyl but has a few extra atoms sticking out of it. Those atoms make a huge difference. Carfentanil is one hundred times more potent — and deadly — than regular fentanyl. N N N N O O Acetyl Fentanyl Acetyl fentanyl was the first fentanyl analogue to appear regularly in the illicit drug supply in the United States. That happened in 2013. Since then there have been many more.

There are hundreds of known fentanyl analogues. Here are just a few that have been identified in seized drugs in recent years.

Fentanyl analogues Description: These images show several fentanyl analogues that have been identified in seized drugs in recent years. N N N N O O Methoxyacetyl Fentanyl O N N N N O O Cyclopropyl Fentanyl O O N N N N O O Benzodioxole Fentanyl N N F N N N N O O 4-Fluorobutyryl Fentanyl O N N N N O O Furanyl Fentanyl N N N N O O Benzylfentanyl N N N N O O Butyryl Fentanyl N N N N O O 3-Methylfentanyl N N N N O O Valeryl fentanyl F N N N N O O meta-Fluorobutyryl fentanyl OH N N N N O O Beta-Hydroxyfentanyl N N N N O O Isobutyryl fentanyl S N N N N O O Thiofentanyl S N N N N O O Alpha-Methyl Thiofentanyl N N N N O O Pivaloyl fentanyl N N N N O O Cyclobutyl fentanyl N N N N O O 3’-Methyl Acetyl Fentanyl N N N N O O Crotonyl fentanyl

Analogues often evade detection because of a scientific Catch-22. When forensic chemists analyze a suspicious-looking powder, they run it through an instrument that generates the molecular “fingerprints” of the chemical compounds present. They then run those fingerprints, called mass spectra, through a database to look for a match. However, they will only get a match if the compound is already listed in their database. New analogues, by definition, are not yet listed, and most forensic labs will be unable to identify them.

“The technology is not very good at identifying unknown unknowns,” Sisco said. 

Most labs, if they detect something new, will have to send a sample to one of a small number of labs that have the sophisticated equipment and rare expertise needed to identify the compound and work out its chemical structure. This delay slows down the response by public health and law enforcement agencies. 

“If people start overdosing and dying from a new drug analogue, authorities need to identify it as quickly as possible,“ said NIST research chemist Aaron Urbas in a news release. “If you want to focus your resources effectively, you need to know what you’re looking for.”

The challenge of identifying analogues is present with many types of drugs beyond fentanyl. Other synthetic opioids also spin off analogues, as do cannabinoids (aka synthetic marijuana), cathinones (aka bath salts), benzodiazepines and others. All can be deadly, and all appear in many forms.

To help labs identify novel substances more quickly, NIST is developing new software tools that partly solve the Catch-22 of drug identification by recognizing subtle patterns in molecular fingerprints. This software can indicate whether an unknown compound is likely to be a new fentanyl analogue, shortening the time it takes to work out its molecular structure and add its fingerprints to chemical identification databases. NIST scientists also regularly update chemical identification databases with new compounds and have developed online platforms where forensic and research chemists can share information on emerging substances more quickly.

What NIST Is Doing

Free Software Can Help Spot New Forms of Fentanyl and Other Illegal Drugs

A new software tool from NIST can help forensic chemists identify new fentanyl analogues.

NIST Adds New 'Fingerprints' to Chemical Identification Database

The NIST Mass Spectral Library has expanded to include new human and plant metabolites, variants of fentanyl and other synthetic drugs.

Data-Sharing Website May Speed Response to New Illegal Drugs

The NPS data hub is a website where law enforcement and other chemists can share data on new drug variants, including chemical structures and signatures.

Quality Control for SWGDRUG

NIST chemists ensure the quality and accuracy of the data in quarterly updates to SWGDRUG, an authoritative database of identifying information for illegal drugs.

Part IV:
Keeping It Real

Public health and law enforcement officials today face a growing and fast-changing challenge. To do their jobs — and to save lives — they need to be able to detect and identify a growing number of new and potent drugs. 

Meeting this challenge requires new thinking in terms of analytical chemistry. NIST is developing new approaches in close collaboration with the experts, at the Maryland State Police Department and other agencies, who encounter these drugs every day. NIST program manager Marcela Najarro explains why this type of close collaboration is essential to move the science forward.

NIST program manager Marcela Najarro describes how NIST scientists collaborate closely with forensic chemists in the field and why this collaboration is so essential to the development of useful solutions.

These collaborations are expanding to include other agencies facing similar challenges, and this page will be updated as new projects come online. Unfortunately, as the overdose epidemic intensifies, the research needs in forensic chemistry are growing. Today the main culprit is fentanyl. But many synthetic drugs are similarly dangerous and difficult to control. And new synthetic drugs, still unknown, will emerge in coming years.

The opioid crisis presents analytical chemistry challenges that are great and constantly changing. But NIST is working with forensic labs to help them meet those challenges — safely, efficiently and reliably.

Technical Contact


Marcela Najarro
marcela.najarro@nist.gov

 

Created April 16, 2020, Updated April 20, 2021