The prominence of fentanyl and fentanyl analogues or Fentanyl Related Substances (FRS) has driven a nationwide crisis of opioid overdoses, which significantly presents an issue for public health and safety. Originally developed for medical purposes, fentanyl and FRS have become critical contributors to opioid overdose deaths due to their distribution, availability, and potency. This study examined toxicodynamic properties between butyrylcholinesterase (BChE) and fentanyl analogues via Ellman's assay. The enzymatic function of BChE was significantly inhibited by each of the 5 fentanyl analogues tested, which indicates the potential for utilization of this interaction. This reaction can be immobilized for a portable, single-use kit to detect FRS directly from any surface on-site. This would immensely benefit society by reducing the frequency of exposure and overdoses by providing additional safety measures to law enforcement and first responders.

Cannabis Facility International Clinical Research Centre St Anne's University Hospital Brno 60200 Czech Republic

Center for Pain Management Department of Anesthesiology and Intensive Care St Anne's University Hospital Brno 60200 Czech Republic

Department of Environmental Toxicology The Institute for Forensic Science Texas Tech University 1207 Gilbert Drive Lubbock Texas 79416 United States

Department of Natural Drugs Faculty of Pharmacy Masaryk University Palackého 1946 1 61200 Brno Czech Republic

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Stanley T. H. The Fentanyl Story. Journal of Pain. 2014, 15 (12), 1215–1226. 10.1016/j.jpain.2014.08.010. PubMed DOI

Tennyson K. M.; Ray C. S.; Maass K. T.. Fentanyl and Fentanyl Analogues: Federal Trends and Trafficking Patterns. United States Sentencing Commission, 2021; https://www.ussc.gov/sites/default/files/pdf/research-and-publications/research-publications/2021/20210125_Fentanyl-Report.pdf

Choińska M. K.; Šestáková I.; Hrdlička V.; Skopalová J.; Langmaier J.; Maier V.; Navrátil T. Electroanalysis of Fentanyl and Its New Analogs: A Review. Biosensors. 2022, 12 (1), 26.10.3390/bios12010026. PubMed DOI PMC

Drug scheduling. DEA. n.d., https://www.dea.gov/drug-information/drug-scheduling.

O’Donnell J. K.; Halpin J.; Mattson C. L.; Goldberger B. A.; Gladden M. Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700—10 States, July–December 2016. CDC 2017, 66 (44), 1197–1202. 10.15585/mmwr.mm6643e1. PubMed DOI PMC

U.S. overdose deaths in 2021 increased half as much as in 2020 - but are still up 15%. CDC.2022, https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2022/202205.htm.

DEA warns of increase in Mass-Overdose events involving deadly fentanyl. DEA.2022, https://www.dea.gov/press-releases/2022/04/06/dea-warns-increase-mass-overdose-events-involving-deadly-fentanyl.

Penichet-Paul C.Illicit Fentanyl and Drug Smuggling at the U.S.-Mexico Border: An Overview. National Immigration Forum, 2023; https://immigrationforum.org/article/illicit-fentanyl-and-drug-smuggling-at-the-u-s-mexico-border-an-overview/

DEA warning to police and public: Fentanyl exposure kills. DEA.2015, https://ndews.umd.edu/sites/ndews.umd.edu/files/DEA%20Fentanyl.pdf.

Opioid overdose. WHO.2023, https://www.who.int/news-room/fact-sheets/detail/opioid-overdose.

Year in Review: DEA innovates to fight Fentanyl. DEA.2024, https://www.dea.gov/press-releases/2024/01/18/year-review-dea-innovates-fight-fentanyl.

Fentanyl Facts.CDC.2024, https://www.cdc.gov/stop-overdose/caring/fentanyl-facts.html.

Remediation of fentanyl contaminated indoor environments. EPA.2024, https://www.epa.gov/sciencematters/remediation-fentanyl-contaminated-indoor-environments.

What you can do to test for Fentanyl. CDC. n.d., https://www.cdc.gov/stop-overdose/safety/index.html.

Crocombe R. A.; Giuntini G.; Schiering D. W.; Profeta L. T. M.; Hargreaves M. D.; Leary P. E.; Brown C. D.; Chmura J. W. Field-portable detection of fentanyl and its analogs: A review. Journal of Forensic Sciences 2023, 68 (5), 1570–1600. 10.1111/1556-4029.15355. PubMed DOI

Nurulain S. M.; Adem A.; Munir S.; Habib R.; Awan S.; Anwar F.; Batool S. Butyrylcholinesterase in Substance Abuse: An Overview. Neurophysiology 2020, 52 (2), 145–158. 10.1007/s11062-020-09864-3. DOI

Çokuğraş A. N. Butyrylcholinesterase: Structure and Physiological Importance. Turk J. Biochem. 2003, 28 (2), 54–61.

Taylor P.; Camp S.; Radić Z. Acetylcholinesterase. Encyclopedia of Neuroscience 2009, 5–7. 10.1016/B978-008045046-9.01132-3. DOI

Zheng F.; Zhan C. Cocaine hydrolases designed from butyrylcholinesterase. In Biologics to Treat Substance Use Disorders 2016, 187–225. 10.1007/978-3-319-23150-1_12. DOI

Taghizadehghalehjoughi A.; Naldan M. E.; Yeni Y.; Genc S.; Hacimuftuoglu A.; Isik M.; Necip A.; Bolat İ.; Yildirim S.; Beydemir S.; Baykan M. Effect of fentanyl and remifentanil on neuron damage and oxidative stress during induction neurotoxicity. Journal of Cellular and Molecular Medicine 2024, 28 (4), e1811810.1111/jcmm.18118. PubMed DOI PMC

Komersová A.; Komers K.; Čegan A. New findings about Ellman’s method to determine cholinesterase activity. Zeitschrift Für Naturforschung C 2007, 62 (1–2), 150–154. 10.1515/znc-2007-1-225. PubMed DOI

Absorbance measurements: BMG LABTECH. 2024, https://www.bmglabtech.com/en/absorbance/.

Dogruer Erkok S.; Hernandez E.; Cruz J.; Mebel A. M.; McCord B. Differentiating structurally similar fentanyl analogs by comparing density Functional Theory (DFT) calculations and Surface-Enhanced Raman Spectroscopy (SERS) results. Appl. Spectrosc. 2024, 78 (7), 667.10.1177/00037028241246010. PubMed DOI