{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:42:30Z","timestamp":1790754150636,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T00:00:00Z","timestamp":1536105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Testing and Analysis"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Designer benzodiazepines have emerged as recreational drugs. They are available via the Internet without control and are found in the form of falsified (fake) medicines. For some of them, limited information concerning their effects, their toxicity, and their detection in bio fluids is available in the literature. For others, nothing has been published, as in the case of flunitrazolam (FNTZ). To gain preliminary data on its elimination parameters in urine and to investigate its metabolism, one of the authors ingested one pink tablet bought on the Internet, after confirming the absence of other compounds and agreement with the labeled dosage (0.25\u00a0mg) by nuclear magnetic resonance (NMR). A software algorithm (MetaboLynx, Waters, Milford, MA, USA) was used to predict FNTZ biotransformation and four potential metabolites were proposed: 4\u2010hydroxy\u2010FNTZ, desnitro\u2010FNTZ, 7\u2010amino\u2010FNTZ, and 7\u2010acetamido\u2010FNTZ. Urine samples were collected over 72\u00a0hours following oral administration of one tablet. After liquid\/liquid extraction at pH\u00a09.5, FNTZ concentrations were determined using ultra performance liquid chromatography\u2013triple quadrupole\u2013mass spectrometry (UPLC\u2013QqQ\u2013MS\/MS). FNTZ remained detectable in hydrolyzed urine for 21\u00a0hours after ingestion, with concentrations ranging between 1 and 18\u00a0ng\/mL. About 3% of the initial dose was excreted in urine as total unchanged FNTZ during this period. In vitro experiments (HLM incubations) were performed using ultra performance liquid chromatography\u2013quadrupole time of flight\u2010mass spectrometry (UPLC\u2013QTOF\u2013MS) in order to investigate the potential CYP\u2010 and UGT\u2010dependent metabolites where only 7\u2010amino\u2010FNTZ was detected as the only metabolite. However, in the urine specimens, desnitro\u2010FNTZ, 7\u2010acetamido\u2010FNTZ and 7\u2010amino\u2010FNTZ were the main detected compounds. The identification of FNTZ metabolites dramatically improves the detection windows of the drug up to 37\u00a0hours.<\/jats:p>","DOI":"10.1002\/dta.2480","type":"journal-article","created":{"date-parts":[[2018,8,14]],"date-time":"2018-08-14T23:58:12Z","timestamp":1534291092000},"page":"223-229","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Detection of the designer benzodiazepine flunitrazolam in urine and preliminary data on its metabolism"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1117-0887","authenticated-orcid":false,"given":"Alice","family":"Ameline","sequence":"first","affiliation":[{"name":"Institut de m\u00e9decine l\u00e9gale  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1234-5167","authenticated-orcid":false,"given":"Camille","family":"Richeval","sequence":"additional","affiliation":[{"name":"CHU Lille, Unit\u00e9 Fonctionnelle de Toxicologie  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Michel","family":"Gaulier","sequence":"additional","affiliation":[{"name":"CHU Lille, Unit\u00e9 Fonctionnelle de Toxicologie  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010S\u00e9bastien","family":"Raul","sequence":"additional","affiliation":[{"name":"Institut de m\u00e9decine l\u00e9gale  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4174-5362","authenticated-orcid":false,"given":"Pascal","family":"Kintz","sequence":"additional","affiliation":[{"name":"Institut de m\u00e9decine l\u00e9gale  Strasbourg France"},{"name":"X\u2010Pertise Consulting, Oberhausbergen  France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,5]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2016_34"},{"key":"e_1_2_5_3_1","first-page":"1","article-title":"Reports of adverse events associated with use of novel psychoactive substances, 2013\u20102016: a review","volume":"28","author":"Logan BK","year":"2017","journal-title":"J Anal Toxicol"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2017.274662"},{"key":"e_1_2_5_5_1","unstructured":"European Monitoring Centre for Drugs and Drug Addiction(2018) Fentanils and synthetic cannabinoids: driving greater complexity into the drug situation. An update from the EU Early Warning System (June 2018) Publications Office of the European Union Luxembourg.http:\/\/www.emcdda.europa.eu\/system\/files\/publications\/8870\/2018\u20102489\u2010td0118414enn.pdfAccessed on 5 March 2018."},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/wps.20236"},{"key":"e_1_2_5_7_1","first-page":"5","article-title":"Les \u00ab designer benzodiazepines \u00bb : qu'en sait\u2010on aujourd'hui?","volume":"30","author":"Chetraru E","year":"2018","journal-title":"Toxicol Anal Clin"},{"issue":"35","key":"e_1_2_5_8_1","first-page":"A4900","article-title":"Choosing the correct benzodiazepine: mechanism of action and pharmacokinetics","volume":"155","author":"Vinkers CH","year":"2012","journal-title":"Ned Tijdschr Geneeskd"},{"issue":"2","key":"e_1_2_5_9_1","first-page":"214","article-title":"Benzodiazepine pharmacology and central nervous system\u2010mediated effects","volume":"13","author":"Griffin CE","year":"2013","journal-title":"The Ochsner J"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1455072517706304"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.2203"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.2099"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389201018666171122124401"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac981422i"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.1865"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/1872312811666170407164216"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-016-0040-x"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.2243"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.2146"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.1628"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-016-9439-6"}],"container-title":["Drug Testing and Analysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fdta.2480","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dta.2480","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T08:39:28Z","timestamp":1760344768000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/dta.2480"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,5]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1002\/dta.2480"],"URL":"https:\/\/doi.org\/10.1002\/dta.2480","archive":["Portico"],"relation":{},"ISSN":["1942-7603","1942-7611"],"issn-type":[{"value":"1942-7603","type":"print"},{"value":"1942-7611","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,5]]},"assertion":[{"value":"2018-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}