{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:25:00Z","timestamp":1790443500071,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T00:00:00Z","timestamp":1533081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Detection of new highly potent synthetic opioids is challenging as new compounds enter the market. Here we present a novel screening method for the detection of opiates and (synthetic) opioids based on their activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A cell-based system was set up in which activation of the \u03bc-opioid receptor (MOR) led to recruitment of \u03b2-arrestin 2, resulting in functional complementation of a split NanoLuc luciferase and allowing readout via bioluminescence. Assay performance was evaluated on 107 postmortem blood samples. Blood (500 \u03bcL) was extracted via solid-phase extraction. Following evaporation and reconstitution in 100 \u03bcL of Opti-MEM\u00ae I, 20 \u03bcL was analyzed in the bioassay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>In 8 samples containing synthetic opioids, in which no positive signal was obtained in the bioassay, quadrupole time-of-flight mass spectrometry revealed the MOR antagonist naloxone, which can prevent receptor activation. Hence, further evaluation did not include these samples. For U-47700 (74.5\u2013547 ng\/mL) and furanyl fentanyl (&amp;lt;1\u201338.8 ng\/mL), detection was 100% (8\/8) for U-47700 and 95% (21\/22) for furanyl fentanyl. An analytical specificity of 93% (55\/59) was obtained for the opioid negatives. From an additional 10 samples found to contain other opioids, 5 were correctly scored positive. Nondetection in 5 cases could be explained by very low concentrations (&amp;lt;1 ng\/mL alfentanil\/sufentanil) or presence of inactive enantiomers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>The MOR reporter assay allows rapid identification of opioid activity in blood. Although the cooccurrence of opioid antagonists is currently a limitation, the bioassay's high detection capability, specificity, and untargeted nature may render it a useful first-line screening tool to investigate potential opioid intoxications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1373\/clinchem.2018.289496","type":"journal-article","created":{"date-parts":[[2018,5,18]],"date-time":"2018-05-18T12:25:34Z","timestamp":1526646334000},"page":"1221-1229","source":"Crossref","is-referenced-by-count":55,"title":["Activity-Based Concept to Screen Biological Matrices for Opiates and (Synthetic) Opioids"],"prefix":"10.1093","volume":"64","author":[{"given":"Annelies","family":"Cannaert","sequence":"first","affiliation":[{"name":"Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium"},{"name":"Laboratory of Toxicology, National Institute of Criminalistics and Criminology, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Vasudevan","sequence":"first","affiliation":[{"name":"Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Friscia","sequence":"first","affiliation":[{"name":"The Center for Forensic Science Research and Education, Fredric Rieders Family Foundation, Willow Grove, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda L A","family":"Mohr","sequence":"first","affiliation":[{"name":"The Center for Forensic Science Research and Education, Fredric Rieders Family Foundation, Willow Grove, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M R","family":"Wille","sequence":"first","affiliation":[{"name":"Laboratory of Toxicology, National Institute of Criminalistics and Criminology, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe P","family":"Stove","sequence":"first","affiliation":[{"name":"Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,8,1]]},"reference":[{"key":"2020022606033797800_B1","doi-asserted-by":"publisher","article-title":"Fentanyl, fentanyl analogs and novel synthetic opioids: a comprehensive review","author":"Armenian","DOI":"10.1016\/j.neuropharm.2017.10.016"},{"key":"2020022606033797800_B2","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/jat\/bkx031","article-title":"Reports of adverse events associated with use of novel psychoactive substances, 2013\u20132016: a review","volume":"41","author":"Logan","year":"2017","journal-title":"J Anal Toxicol"},{"key":"2020022606033797800_B3","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1097\/ADM.0000000000000324","article-title":"Misuse of novel synthetic opioids: a deadly new trend","volume":"11","author":"Prekupec","year":"2017","journal-title":"J Addict Med"},{"key":"2020022606033797800_B4","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3389\/fpsyt.2017.00110","article-title":"An expanding world of novel psychoactive substances: opioids","volume":"8","author":"Zawilska","year":"2017","journal-title":"Front Psychiatry"},{"key":"2020022606033797800_B5","article-title":"European drug report 2017: trends and developments","author":"EMCDDA"},{"key":"2020022606033797800_B6","article-title":"Centers for Disease Control and Prevention (CDC), National Center of Health Statistics (NCHS)","journal-title":"Opioid data analysis"},{"issue":"Pt B","key":"2020022606033797800_B7","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.neuropharm.2013.08.028","article-title":"15 years of genetic approaches in vivo for addiction research: opioid receptor and peptide gene knockout in mouse models of drug abuse","volume":"76","author":"Charbogne","year":"2014","journal-title":"Neuropharmacology"},{"key":"2020022606033797800_B8","first-page":"658","author":"Williams","year":"2013","journal-title":"Foye's principles of medicinal chemistry, central analgesics"},{"key":"2020022606033797800_B9","first-page":"313","article-title":"Validation of the neogen(r) fentanyl ELISA kit for blood and urine","volume":"41","author":"Tiscione","year":"2017","journal-title":"J Anal Toxicol"},{"key":"2020022606033797800_B10","doi-asserted-by":"crossref","first-page":"9527","DOI":"10.1021\/acs.analchem.7b02552","article-title":"Activity-based detection of consumption of synthetic cannabinoids in authentic urine samples using a stable cannabinoid reporter system","volume":"89","author":"Cannaert","year":"2017","journal-title":"Anal Chem"},{"key":"2020022606033797800_B11","doi-asserted-by":"crossref","first-page":"11476","DOI":"10.1021\/acs.analchem.6b02600","article-title":"Detection and activity profiling of synthetic cannabinoids and their metabolites with a newly developed bioassay","volume":"88","author":"Cannaert","year":"2016","journal-title":"Anal Chem"},{"key":"2020022606033797800_B12","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1373\/clinchem.2017.285361","article-title":"Activity-based detection of cannabinoids in serum and plasma samples","volume":"64","author":"Cannaert","year":"2018","journal-title":"Clin Chem"},{"key":"2020022606033797800_B13","first-page":"709","article-title":"Analysis of novel synthetic opioids U-47700, U-50488 and furanyl fentanyl by LC-MS\/MS in postmortem casework","volume":"40","author":"Mohr","year":"2016","journal-title":"J Anal Toxicol"},{"key":"2020022606033797800_B14","doi-asserted-by":"crossref","first-page":"7157","DOI":"10.1073\/pnas.95.12.7157","article-title":"Role for G protein-coupled receptor kinase in agonist-specific regulation of mu-opioid receptor responsiveness","volume":"95","author":"Zhang","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020022606033797800_B15","doi-asserted-by":"crossref","first-page":"19021","DOI":"10.1074\/jbc.271.32.19021","article-title":"Morphine activates opioid receptors without causing their rapid internalization","volume":"271","author":"Keith","year":"1996","journal-title":"J Biol Chem"},{"key":"2020022606033797800_B16","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1124\/mol.66.1.106","article-title":"Relative opioid efficacy is determined by the complements of the G protein-coupled receptor desensitization machinery","volume":"66","author":"Bohn","year":"2004","journal-title":"Mol Pharmacol"},{"key":"2020022606033797800_B17","first-page":"1","article-title":"The use of in vitro and in silico technologies for predicting human pharmacology and toxicology of carfentanil","author":"Feasel","year":"2017"},{"key":"2020022606033797800_B18","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/S0022-3565(24)29586-0","article-title":"Comparison of pharmacological activities of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist","volume":"297","author":"Huang","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"2020022606033797800_B19","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.annemergmed.2016.06.014","article-title":"Fentanyl and a novel synthetic opioid U-47700 masquerading as street \u201cNorco\u201d in central California: a case report","volume":"69","author":"Armenian","year":"2017","journal-title":"Ann Emerg Med"},{"key":"2020022606033797800_B20","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1080\/15563650.2016.1209763","article-title":"Two cases of intoxication with new synthetic opioid, U-47700","volume":"55","author":"Domanski","year":"2017","journal-title":"Clin Toxicol (Phila)"},{"key":"2020022606033797800_B21","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1007\/s00414-017-1593-7","article-title":"Postmortem concentration distribution in fatal cases involving the synthetic opioid U-47700","volume":"131","author":"Dziadosz","year":"2017","journal-title":"Int J Legal Med"},{"key":"2020022606033797800_B22","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1093\/jat\/bkx060","article-title":"Multiple drug-toxicity involving novel psychoactive substances, 3-fluorophenmetrazine and U-47700","volume":"41","author":"Ellefsen","year":"2017","journal-title":"J Anal Toxicol"},{"key":"2020022606033797800_B23","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1002\/dta.1984","article-title":"The first reported fatality associated with the synthetic opioid 3,4-dichloro-n-[2-(dimethylamino)cyclohexyl]-n-methylbenzamide (U-47700) and implications for forensic analysis","volume":"8","author":"Elliott","year":"2016","journal-title":"Drug Test Anal"},{"key":"2020022606033797800_B24","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1080\/15563650.2016.1209767","article-title":"A case of U-47700 overdose with laboratory confirmation and metabolite identification","volume":"55","author":"Jones","year":"2017","journal-title":"Clin Toxicol (Phila)"},{"key":"2020022606033797800_B25","first-page":"158","article-title":"A fatality related to the synthetic opioid U-47700: postmortem concentration distribution","volume":"41","author":"McIntyre","year":"2017","journal-title":"J Anal Toxicol"},{"key":"2020022606033797800_B26","first-page":"1","article-title":"U-47700: a not so new opioid","author":"Rohrig","year":"2017","journal-title":"J Anal Toxicol"},{"key":"2020022606033797800_B27","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s12024-016-9795-8","article-title":"Comparing fatal cases involving U-47700","volume":"12","author":"Ruan","year":"2016","journal-title":"Forensic Sci Med Pathol"},{"key":"2020022606033797800_B28","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1080\/15563650.2016.1209764","article-title":"Near death from a novel synthetic opioid labeled U-47700: emergence of a new opioid class","volume":"55","author":"Schneir","year":"2017","journal-title":"Clin Toxicol (Phila)"},{"key":"2020022606033797800_B29","first-page":"40","article-title":"Two fatalities involving the use of the synthetic opioid u-47700","author":"Spargo","year":"2016","journal-title":"ToxTalk"},{"key":"2020022606033797800_B30","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1080\/15563650.2016.1240806","article-title":"Synthetic agents off the darknet: a case of U-47700 and phenazepam abuse","volume":"55","author":"Vo","year":"2017","journal-title":"Clin Toxicol (Phila)"},{"key":"2020022606033797800_B31","first-page":"242","article-title":"Postmortem and toxicological findings in a series of furanylfentanyl-related deaths","volume":"41","author":"Guerrieri","year":"2017","journal-title":"J Anal Toxicol"},{"key":"2020022606033797800_B32","doi-asserted-by":"crossref","first-page":"904","DOI":"10.15585\/mmwr.mm6634a3","article-title":"Overdose deaths related to fentanyl and its analogs\u2014Ohio, January\u2013February 2017","volume":"66","author":"Daniulaityte","year":"2017","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2020022606033797800_B33","first-page":"21","article-title":"EMCDDA\u2013Europol joint report on a new psychoactive substance: N-phenyl-n-[1-(2-phenylethyl)piperidin-4-yl]-furan-2-carboxamide (furanylfentanyl). EMCDDA\u2013Europol Joint Report on a new psychoactive substance: N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]-furan-2-carboxamide (furanylfentanyl)","author":"European Monitoring Centre for Drugs and Drug Addiction","year":"2017"},{"key":"2020022606033797800_B34","doi-asserted-by":"crossref","first-page":"324","DOI":"10.3109\/15563650.2016.1139715","article-title":"Intoxications involving the fentanyl analogs acetylfentanyl, 4-methoxybutyrfentanyl and furanylfentanyl: results from the Swedish STRIDA project","volume":"54","author":"Helander","year":"2016","journal-title":"Clin Toxicol (Phila)"},{"key":"2020022606033797800_B35","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.15585\/mmwr.mm6537a6","article-title":"Notes from the field: furanyl-fentanyl overdose events caused by smoking contaminated crack cocaine\u2014Br Columbia, Canada, July 15\u201318, 2016","volume":"65","author":"Klar","year":"2016","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2020022606033797800_B36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11419-017-0371-z","article-title":"Furanylfentanyl: another fentanyl analogue, another hazard for public health","volume":"36","author":"Misailidi","year":"2018","journal-title":"Forensic Toxicol"},{"key":"2020022606033797800_B37","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1093\/jat\/bkx037","article-title":"Fatalities involving carfentanil and furanyl fentanyl: two case reports","volume":"41","author":"Swanson","year":"2017","journal-title":"J Anal Toxicol"},{"issue":"229","key":"2020022606033797800_B38","first-page":"85873","article-title":"Schedules of controlled substances: temporary placement of furanyl fentanyl into schedule I","volume":"81","author":"Drug Enforcement Administration","year":"2016","journal-title":"Final order"},{"issue":"219","key":"2020022606033797800_B39","first-page":"79389","article-title":"Schedules of controlled substances: placement of U\u201347700 into schedule I","volume":"81","author":"Drug Enforcement Administration","year":"2016","journal-title":"Final order"},{"key":"2020022606033797800_B40","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s00228-008-0570-y","article-title":"Role of active metabolites in the use of opioids","volume":"65","author":"Coller","year":"2009","journal-title":"Eur J Clin Pharmacol"}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/64\/8\/1221\/32642415\/clinchem1221.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/64\/8\/1221\/32642415\/clinchem1221.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T12:38:04Z","timestamp":1751632684000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/64\/8\/1221\/5608949"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,1]]},"references-count":40,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2018,8,1]]},"published-print":{"date-parts":[[2018,8,1]]}},"URL":"https:\/\/doi.org\/10.1373\/clinchem.2018.289496","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,8,1]]},"published":{"date-parts":[[2018,8,1]]}}}