In 2023, the U.S. Drug Enforcement Agency (DEA) seized over 79.5 million fentanyl-laced pills and 12,000 lbs. of fentanyl powder, amounting to the equivalent of over 376.7 million lethal doses – and seizures have more than doubled in recent years. Likewise, in 2023, the U.S. Customs and Borders Protection (CBP) seized 27,000 lbs. of fentanyl, increasing from 11,200 lbs. in 2021. Consequently, opioid overdoses reached an all-time high at over 110,000 in 2023 and continue to increase. The impact of the deadly opioid epidemic does not stop at overdoses – it poses life-threatening exposure to first responders who arrive on scene. Unfortunately, the drug’s ever-changing chemical structure makes it more deadly and addictive as well as more challenging to detect. For the scientific community, addressing this threat is an all-disciplines-on-deck situation – from chemistry and biology to computing and predictive analytics. Through science and technology, scientists are forging paths toward better detection to improve protection for first responders in the field. Optimizing detection strategies and advancing understanding of the capabilities and limitations of commercial-off-the-shelf products is giving first responders a larger toolset to make decisions in unknown circumstances. Increasing spectral reference libraries to include fentanyl, fentanyl analogs, and adulterated drugs allows for better detection and chemical identification, especially in more complex sample mixtures.
Understanding Emerging Challenges and Hazards
Fentanyl is a synthetic opioid that has hundreds of millions of possible chemical variants, which are known as analogs. Its intended use is as an analgesic or pain reliever. Unfortunately, it is at high risk for addiction and dependence and is highly abused by trafficking. The criminals behind such drugs are constantly modifying compounds to create substances that evade detection while packing an ever-addictive (and often deadly) punch. These substances are not always in pure form and are frequently mixed with cutting agents (e.g., sugars, lidocaine, xylazine, caffeine, acetaminophen, and other drugs) that can interfere with detection. Modified fentanyl analogs can be up to 100 times more potent than fentanyl itself and, therefore, more dangerous to first responders exposed to them in the field, either by direct encounter with illicit materials and drug paraphernalia on-scene or with individuals under the influence of these substances.
The creation of these illicit materials is literally out of control. Quality controls are unlikely in clandestine laboratories, the sites where drugs like fentanyl are illegally manufactured, often with improvised materials and uncontrolled operations. This means the contents and percentages of each component may vary from pill to pill, even in the same batch. Currently, xylazine, a non-opioid tranquilizer not approved for human use, is one of the rising adulterants. Furthermore, one pill or powdered sample may not represent what the rest of the seized products contain. An estimated seven out of 10 DEA-seized pills in 2023 contained a lethal dose of fentanyl, though this cannot be determined visually. While 2 mg of fentanyl is a potentially lethal dose, cutting agents can alter the potency of the fentanyl or fentanyl analog. It becomes more difficult to detect fentanyl or related analogs when they are present in smaller percentages and cutting agents or adulterant features mask the signal. First responders need to have an understanding of their equipment limitations and strengths and may need to use several systems or reachback analysis depending on the circumstance.
The unknowns create challenges with the antidote as well. For example, Naloxone (Narcan) is the established antidote for opioid overdoses. However, its effectiveness is person-dependent based on several physical and physiological factors such as height, weight, history of drug use, and opioid tolerance. Additionally, the specific analog and potential cutting agents may also play a role in antidote effectiveness, especially when the cutting agents in question are not opioids. Drug mixtures adulterated with various cutting agents cause a greater challenge for detection and target identification when compared to the pure form. This in turn creates greater hazards for the first responders who may be exposed to illicit materials present at crime scenes or individuals under the influence of unknown drug mixtures.
Compounding the threat of exposure is the challenge that detection equipment manufacturers struggle to keep pace with the ever-changing makeup of these illicit substances. With new forms of the drug appearing constantly, scientists, first responders, and equipment manufacturers may feel as if they cannot possibly know exactly what they are looking for – but new research and scientific discovery are shedding light on potential solutions.
Expanding Detection Strategies and Technologies
Confronting fentanyl at this nexus of unknowns is a daunting and enduring task, but detection capabilities have improved over the years. Common commercial-off-the-shelf products for fentanyl detection include optical instrumentation such as Fourier transform infrared and Raman spectroscopy. These products require little to no sample handling and offer a quick response time. However, due to spectral saturation of adulterants, optical instruments struggle to identify low levels of fentanyl within mixtures. Mass-based instrumentation offers higher sensitivity to fentanyl mixtures but often requires sample handling and potential destruction of the sample. Colorimetric and immunoassays are also common products in the field, offering rapid analysis at lower costs than portable instrumentation. However, unlike portable instruments, assays lack analog specificity and, in the case of colorimetric assays, are privy to false positives and negatives.
The more scientists understand these emerging substances and the equipment to detect them, the greater protection and safety they can deliver to the first responder community encountering this threat. This is why scientists at the Pacific Northwest National Laboratory (PNNL) and the Department of Homeland Security (DHS) Science and Technology Directorate (S&T) have been leading projects focused on closing the gap between detection equipment and what responders encounter in the field. These projects include updating standards for, expanding chemical libraries used by, and ultimately assessing detection equipment.
For example, it helps when there is consistency in how to safely and efficiently use equipment, which can be achieved through standards. Bringing together more than 100 scientists, first responders, drug enforcement officials, equipment manufacturers, and others to help ASTM International develop three new laboratory standards:
- Two addressed the performance of equipment and methods to test for fentanyl and related compounds in the field.
- One provided a guide for first responders encountering fentanyl in the field.
This work benefitted from considerable input from first responders and strong relationships, in part through the Northwest Regional Technology Center.
It also helps when equipment has the most up-to-date information. In the case of synthetic opioid detection, this is in the form of spectral libraries used by detection equipment. These spectral libraries are like a set of chemical fingerprints. A bigger spectral library widens the aperture on substances a first responder can identify during an encounter. PNNL and DHS S&T scientists updated the libraries for portable instruments that give first responders insight into their encounters. They added about 50 chemical structures, including information on drugs like heroin, cocaine, and methamphetamine. The expansion of spectral libraries is a constant need as trends change in the compounds encountered in field and is not limited to only synthetic opioids. As these trends become apparent, researchers and vendors work to update libraries to include such chemicals.
This work came together in a rigorous assessment of detection equipment to understand the limitations of commercial products commonly used by the first responder community. Together, the team safely prepared, validated, measured, and analyzed the necessary samples and the corresponding data. Scientists tested and evaluated 17 detection instruments and eight assays. Test samples included a suite of pure fentanyl analogs, 1 percent and 10 percent fentanyl mixtures, and other pure or mixed compounds created to mimic real-world scenarios. The results are publicly available and can help inform the procurement of field detection systems by DHS partners, first responder agencies, and other end users.
PNNL scientists are even looking at ways to get ahead of detection by using powerful computational chemistry techniques to predict possible fentanyl analogs before reaching the street. This research is part of an effort to reduce reliance on libraries based on the analysis of physical samples. By predicting and ranking chemical structures that may be present in a sample based on fundamental scientific principles, scientists would be able to detect potential threats from other forms of fentanyl or sources earlier without relying on previously known threats.
Protecting the Protectors
The current opioid epidemic is continuously expanding, and so is research and outreach to combat this rapidly evolving threat. The outcomes of this type of research and development benefit first responders and front-line personnel by providing the knowledge needed to adapt and optimize current protocols for existing deployed handheld devices (e.g., combining different technology class detection capabilities when feasible) and to inform future procurements of equipment to improve the safety of first responders and the public. To the extent possible, the results of this work are available to the first responder community to help provide the best tools to detect fentanyl and related compounds. For example, the DHS National Urban Security Technology Laboratory’s System Assessment and Validation for Emergency Responders (SAVER) program regularly publishes the results of focus groups, market surveys, assessments, and more to provide emergency responders with information to inform their procurement decisions. In addition to detection performance or target sensitivity, several other factors must be considered when selecting commercial-off-the-shelf products to deploy during chemical incidents of unknown materials. These factors include (but are not limited to) ease of use, operability when wearing personal protective equipment, ruggedness, response time, sample preparation, and consumption.
Following are several publicly available resources to help stay up to date on standards, technology assessments, and other outreach tackling this threat:
- The following SAVER reports offer detailed information on popular handhelds on the market:
- The following performance assessment tested field-portable detection products against updated compound libraries and testing standards:
- The following ASTM standards were developed to assist first responders with use of field detection equipment:
- ASTM E3243-21 Standard Specification for Field Detection Equipment and Assays Used for Fentanyl and Fentanyl-Related Compounds
- ASTM E3289-21 Standard Guide for Using Equipment and Assays for Field Detection of Fentanyl and Fentanyl-Related Compounds
- ASTM E3290-21 Standard Test Method for Establishing Performance of Equipment and Assays for Field Detection of Fentanyl and Fentanyl-Related Compounds
By providing information ranging from equipment costs to summarized performance data of common field-deployable equipment, scientists hope to enhance public safety and add tools and resources for first responders to easily pull from when faced with difficult and high-risk situations.
Ashley Bradley
Ashley Bradley is a biomedical scientist with a background in analytical chemistry and molecular biology. She graduated from Washington State University magna cum laude with a BS in biochemistry and a double major in genetics. Since joining the Pacific Northwest National Laboratory (PNNL) in 2017, her work has focused on spectroscopic signatures of solid, liquid, and gas-phase samples. Most notably, she has been a key contributor to the liquid signatures effort, playing a major role in collecting important data used in high-fidelity spectral libraries. She is currently a principal investigator for a project that utilizes this capability to expand spectral libraries of instruments used by first responders.
Kristin Omberg
Kristin Omberg is a senior technical advisor in the National Security Directorate at PNNL. Her technical work focuses on developing science and technology solutions that can be deployed in operational environments or used to inform policy decisions. Before joining PNNL, she spent more than 15 years at Los Alamos National Laboratory, where she was a program manager and principal investigator for numerous projects for the DHS and Defense.
