fentanyl is up to 100 times as potent as its cousin morphine<\/a>. Just two milligrams \u2014 the amount that fits on the tip of a pencil \u2014 is potentially lethal, and the United States reported more than 72,000 overdose deaths in 2023 alone. Fentanyl contains no natural ingredients, and underground labs can tweak its structure just enough to avoid detection while retaining its heroinlike effect. That\u2019s made it profitable to lace pills with a powerful substance that many users don\u2019t know they\u2019re consuming.<\/p>\nThe only way experts can know if a pill contains a fentanyl variant is by comparing it to a reference library made by analyzing pure chemical compounds in the lab. But calculations indicate that there are billions of possible forms of fentanyl \u2014 and experts know only about 60,000 of them. Forensic and toxicology labs can\u2019t keep up. \u201cIt\u2019s become a whack-a-mole problem,\u201d says biochemist David Wishart of the University of Alberta in Edmonton, Canada, who wasn\u2019t involved with the work.<\/p>\n
Bioanalytical chemist Tom Metz says, \u201cPure forms are not going to get us where we need to be.\u201d Metz, of Pacific Northwest National Laboratory in Richland, Wash, and his colleagues set out to eliminate the need for traditional reference libraries. In prior work, they used two customized instruments to identify chemical features shared by fentanyl compounds and to distinguish between many unrelated molecules that share fentanyl\u2019s molecular mass.\u00a0<\/p>\n
All fentanyls have a common core chemistry, but labs can vary surrounding chemical groups. \u201cIt\u2019s like a Christmas tree \u2014 nearly always a pine tree of some sort, but each household will decorate it differently,\u201d Metz says. The instruments give clues to the precise elements that make up molecules, how they\u2019re structured and the shape they adopt during analysis.\u00a0<\/p>\n
Now that the researchers knew which measurements would thoroughly profile fentanyls, for the new study they dreamed up a database of hypothetical variants. They computationally broke apart each of the roughly 60,000 known fentanyl and fentanyl-like molecules into a few different fragments, then recombined them to create several billion molecules. Next, they eliminated nonsensical and implausible molecules from their digital catalog, such as ones unlikely to penetrate the brain\u2019s protective barrier. Finally, with help from machine learning, they predicted what real-world chemical measurements of the dreamed-up structures would look like. They combined that data with that of the 60,000 known structures to make their final digital library of over 1 billion analogs.<\/p>\n
The researchers could not test street drugs, so instead they created a mock fentanyl pill with traces of 12 commercially available fentanyl varieties, along with a chemically similar nonopioid decoy, cut with typical street pill ingredients like caffeine. They completed the feature-identifying measurements, then handed the raw data and the computer-generated library to another analytical chemist who\u2019d never seen the mock pill, with a prompt: \u201cWe suspect there\u2019s fentanyl in this sample. Can you tell us which, if any, analogs are in it?\u201d<\/p>\n
The answer was a resounding \u201cYes.\u201d After multiple cycles of narrowing down possible matches, the blinded chemist identified six of the mock pill\u2019s fentanyl components perfectly and narrowed another four down to a few possible candidates each, no pure compound library needed. The remaining two lacked the signatures used for flagging or could not be fully teased apart. The results have not yet been peer-reviewed.<\/p>\n
The approach is a \u201ctremendous first step,\u201d but it relies on customized instruments unavailable to most forensic or national security laboratories, says chemist A. Way Fountain III of the University of South Carolina in Columbia, who wasn\u2019t part of the study. And the technique should be tested with other classes of drugs or molecules to show where improvements are needed, Fountain says.<\/p>\n
Such tests are underway. Among several classes of molecules Metz and his colleagues are studying, they have also identified common features in a new family of lab-made opioids called nitazenes that are becoming prevalent in overdose cases.<\/p>\n
Wishart thinks the work will help modernize the forensic community\u2019s approach for identifying unknown compounds. Relying on a reference library of pure compounds \u201cis still very 19th century thinking,\u201d he says.<\/p>\n
Molecular pharmacologist Gary Miller of Columbia University, who wasn\u2019t involved with the research, agrees. \u201cReference-free identification could be revolutionary from a scientific standpoint,\u201d he says. \u201cThese data demonstrate that the approach can work.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"
Illicit laboratories do a criminally good job of synthesizing new forms of dangerous drugs that slip under the radar, but a new method could spot variants of the powerful opioid drug fentanyl even before they\u2019ve been cataloged by authorities. Measuring a suspicious pill\u2019s traits and comparing them to computer-generated reference values could reveal chemical signatures […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[10],"tags":[],"_links":{"self":[{"href":"https:\/\/www.adviews.info\/news\/index.php?rest_route=\/wp\/v2\/posts\/105104"}],"collection":[{"href":"https:\/\/www.adviews.info\/news\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.adviews.info\/news\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.adviews.info\/news\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.adviews.info\/news\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=105104"}],"version-history":[{"count":0,"href":"https:\/\/www.adviews.info\/news\/index.php?rest_route=\/wp\/v2\/posts\/105104\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.adviews.info\/news\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=105104"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.adviews.info\/news\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=105104"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.adviews.info\/news\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=105104"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}