Complicating the Opioid Epidemic: The Many Fa


image: PNNL scientists are expanding the library of data on known fentanyl compounds. Each addition to the catalog is a step towards safety for law enforcement, paramedics and others.
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Credit: Animation by Sara Levine | Pacific Northwest National Laboratory

RICHLAND, Wash. — While Covid has dominated the headlines for two consecutive years, a different epidemic claims the lives of more than 100,000 Americans each year.

At the heart of the opioid epidemic is fentanyl, the synthetic substance originally designed as a painkiller but turned into a lucrative and deadly street drug.

Beyond the thousands of lives each outbreak claims each month, the two share an important trait: the ability to transform – or be transformed – into something unexpected, a difficult challenge.

The first step to protecting ourselves is simply knowing that a threat exists.

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Fentanyl variants: the threat

Covid has produced variants like Omicron, adept at dodging the body’s defenses.

Fentanyl also has variants – chemical structures that have a greater effect on the body, are more lethal and addictive. Enterprising chemists around the world are busy experimenting in makeshift labs, generating new, illegal forms of the painkiller – estimated to be 100 times more potent in its base form than morphine – in a bid to evade detection , get around the law and make more money.

Scientists at the Department of Energy’s Pacific Northwest National Laboratory estimate that fentanyl has hundreds of millions of possible chemical variants, known as analogues. Every variant that becomes real in the hands of an enterprising chemist is synonymous with risk.

“New forms of drugs are constantly emerging,” said PNNL scientist Richard Ozanich, an analytical chemist who is tackling the fentanyl crisis with funding from the Department of Homeland Security. “That means sometimes we don’t know exactly what we’re looking for; a new form may not yet be on law enforcement’s radar.

Fentanyl library saves lives

First responders rely on databases, commonly referred to as libraries, of the chemical structures of known fentanyl variants. It’s like a set of chemical fingerprints of harmful drugs and other dangerous substances. Keeping the fentanyl library up to date is extremely important. Drug dealers and unscrupulous chemists are constantly modifying compounds in small but substantial ways, enough to create substances that evade detection, allow traffickers to evade prosecution while packing a deadly punch.

Many of the illicit substances that reach the United States come from Mexico and China. Their creators are working on analogs that are more addictive or easier to manufacture. Or they create forms that can be diluted or “cut” more effectively, increasing profits, or used to increase counterfeit pills and other illicit substances.

Each variant that is not listed offers criminals a loophole, an opportunity to circumvent the law.

“Even if a compound isn’t on the list yet, it can kill you,” said Ozanich, who noted that some forms are so potent that an amount as small as a grain of salt can be lethal.

Ozanich leads a project funded by the Department of Homeland Security’s Science and Technology Directorate to help close the gap. His team updates the libraries that police, hazmat teams and other first responders use to identify and understand the hazardous substances they encounter. Police, firefighters and others typically carry handheld instruments that tap into these databases, giving officials instant insight into what they’ve encountered.

PNNL has added about 50 chemical structures to the libraries, which also include information on drugs like heroin, cocaine and methamphetamine.

A larger library reduces the risk of a police officer, firefighter, paramedic, or others encountering a dangerous unknown substance that they cannot identify.

“Law enforcement and other officials need to make decisions quickly in dangerous situations. Should we cordon off the perimeter? Are we safe? Is there a danger to others? making these decisions quickly is central to our efforts,” Ozanich said.

“Knowing what danger you face on the ground allows you to take appropriate action to protect yourself and the public,” he added.

Beyond the Library

Other PNNL scientists are using powerful computers and new computational chemistry techniques to predict possible fentanyl analogs that haven’t even been created yet – possible additions to the library before they’re even in the pipeline. Street. The research is part of an effort to ultimately reduce reliance on a library built from the results of analysis of physical samples.

Instead, PNNL scientists are exploring ways to predict and classify possible chemical structures that may be present in a sample based on an understanding of the fundamental scientific principles involved. from other forms of fentanyl or from other sources, without relying exclusively on what is already known.

Fentanyl research fits perfectly into the wheelhouse of the PNNL to research, detect and measure substances or phenomena of interest. These include explosive residues, noble gases produced during nuclear explosions, dark matter, traces of other illicit drugs, radiation signs and dangerous chemicals such as ricin and sarin. Researchers are actively looking for new ways to detect or, ideally, predict and prevent these threats before they exist.

“This capability boils down to proactive situational awareness, which is the ability to get ahead of the threat in time to help law enforcement and first responders effectively mitigate it,” Kabrena said. Rodda, a senior scientist at PNNL who leads a number of projects to counter chemical threats.

“As this capability matures, we are excited about the potential to move beyond simple recognition of a threat to apply it in new applications to keep people safe,” Rodda added.

Ensure accuracy, safety in the field

The library update is part of a larger two-year project that Ozanich is leading to evaluate the performance of detection equipment used by emergency responders across the country. PNNL brought together 14 manufacturers of 21 key instruments that first responders and others use to detect and measure fentanyl. These instruments cover nearly every form of fentanyl found on the streets today.

Through this effort, the current work of Ozanich and his colleagues will impact nearly every fentanyl incident faced by police and others across the country.

The project is part of another DHS-funded project led by Ozanich focused on fentanyl standards. It brought together more than 100 scientists, first responders, drug enforcement officials, equipment manufacturers and others under the auspices of ASTM International to develop three new laboratory standards. Without proper standards, police officers and paramedics would be at greater risk in the performance of their duties.

Two standards address the performance of equipment and methods for testing fentanyl and related compounds in the field. A third standard is designed as a guide for first responders encountering fentanyl in the field. This standard has benefited from extensive input from first responders, with whom PNNL has a strong relationship, in part through the Northwest Regional Technology Center.

One law enforcement official who has worked with Ozanich is Detective Sergeant Pakorn Patimetha of the New Jersey State Police Hazardous Materials Response Unit.

“Every day we see different varieties of fentanyl mixed in with all types of illicit drugs and pills,” said Patimetha, who majored in biochemistry in college before moving into teaching and then law application. Patimetha estimates that over the past five years, the percentage of narcotics samples sent to the state crime lab containing fentanyl has increased from five percent to more than 90 percent.

“A crime scene can be chaotic. We need to identify fentanyl quickly and accurately in the field to ensure everyone stays safe and dangerous evidence is properly secured,” Patimetha added. “It’s important to keep first responders involved because we can explain what it’s like on the ground, in real-life conditions. Rich gets the first responders involved. We contribute directly to make sure the methods are valid and work the way we need them to work. »


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