{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:39:11Z","timestamp":1792100351042,"version":"4.4.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["CTQ2017-83823-R"],"award-info":[{"award-number":["CTQ2017-83823-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Supramolecular solvents with restricted-access properties (SUPRAS-RAMs) are proposed as a new approach for integrating extraction and sample cleanup in the quantification of benzodiazepines (BDZs) in urine by liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS-MS). The SUPRAS-RAM was synthesized in situ in the urine by the addition of 1-hexanol (154\u2009\u00b5L) and tetrahydrofuran (THF) (600\u2009\u00b5L). BDZ extraction was driven by both hydrogen bonds and dispersion interactions. Removal of proteins and polar macromolecules was performed by the action of the SUPRAS through chemical and physical mechanisms. Phospholipids were removed by precipitation during SUPRAS extract evaporation. A multivariate method was used for the optimization of the extraction process by applying Box\u2013Behnken response surface design. The proposed method was validated according to the guiding principles of the European Commission Decision (2002\/657\/EC). Method detection and quantification limits for the target BDZs were in the intervals 0.21\u20130.85 and 0.67\u20132.79\u2009ng\/mL, respectively. The repeatability and reproducibility (expressed as relative standard deviations) were in the range 2\u20136% and 3\u20138%, respectively. The method enabled the simultaneous extraction of BDZs (recoveries in the range 84\u2013105%) and the removal of matrix effects. The method was applied to the analysis of 13 urine samples using external calibration. Five out of 13 samples tested positive in alprazolam and lorazepam at concentrations in the range 5.4\u201374\u2009ng\/mL. The method allows simple and quick sample treatment with minimal solvent consumption while delivering accurate and precise data.<\/jats:p>","DOI":"10.1093\/jat\/bkab023","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T20:13:50Z","timestamp":1614629630000},"page":"285-294","source":"Crossref","is-referenced-by-count":10,"title":["Interference-Free Method for Determination of Benzodiazepines in Urine Based on Restricted-Access Supramolecular Solvents and LC\u2013MS-MS"],"prefix":"10.1093","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0662-1815","authenticated-orcid":false,"given":"Noelia","family":"Caballero-Casero","sequence":"first","affiliation":[{"name":"Department of Analytical Chemistry, Institute of Fine Chemistry and Nanochemistry, Universidad de C\u00f3rdoba, Marie Curie-Annex Building, Campus de Rabanales, C\u00f3rdoba 14071, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libargachew D","family":"Mihretu","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Institute of Fine Chemistry and Nanochemistry, Universidad de C\u00f3rdoba, Marie Curie-Annex Building, Campus de Rabanales, C\u00f3rdoba 14071, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soledad","family":"Rubio","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Institute of Fine Chemistry and Nanochemistry, Universidad de C\u00f3rdoba, Marie Curie-Annex Building, Campus de Rabanales, C\u00f3rdoba 14071, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"key":"2022032114033123800_R1","article-title":"The misuse of benzodiazepines among high-risk opioid users in Europe","volume-title":"Perspectives on Drugs, 2018","author":"EMCDDA","year":"2018"},{"key":"2022032114033123800_R2","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1176\/appi.ps.201800321","article-title":"Benzodiazepine use and misuse among adults in the United States","volume":"70","author":"Maust","year":"2019","journal-title":"Psychiatric Services"},{"key":"2022032114033123800_R3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jflm.2020.102020","article-title":"Violence against women and drug-facilitated sexual assault (DFSA): a review of the main drugs","volume":"74","author":"Costa","year":"2020","journal-title":"Journal of Forensic and Legal Medicine"},{"key":"2022032114033123800_R4","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.jflm.2012.10.005.","article-title":"Concentrations of drugs determined in blood samples collected from suspected drugged drivers in England and Wales","volume":"20","author":"Burch","year":"2013","journal-title":"Journal of Forensic and Legal Medicine"},{"key":"2022032114033123800_R5","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.jpba.2015.02.017.","article-title":"Analytical methodologies for the determination of benzodiazepines in biological samples","volume":"113","author":"Persona","year":"2015","journal-title":"Journal of Pharmaceutical and Biomedical Analysis"},{"key":"2022032114033123800_R6","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/978-1-4939-8823-5_3","article-title":"Analysis of benzodiazepines for drug-facilitated assaults and abuse settings (urine)","volume":"1872","author":"Drummer","year":"2019","journal-title":"Methods in Molecular Biology"},{"key":"2022032114033123800_R7","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.clinms.2018.08.004","article-title":"Urine analysis of 28 designer benzodiazepines by liquid chromatography\u2013high-resolution mass spectrometry","volume":"10","author":"Pettersson Bergstrand","year":"2018","journal-title":"Clinical Mass Spectrometry"},{"key":"2022032114033123800_R8","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1093\/jat\/bkaa072","article-title":"Development and validation of an LC\u2013MS-MS method for the detection of 40 benzodiazepines and three Z-drugs in blood and urine by solid-phase extraction","volume":"44","author":"Sofalvi","year":"2020","journal-title":"Journal of Analytical Toxicology"},{"key":"2022032114033123800_R9","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1093\/jat\/30.8.524","article-title":"LC-MS-(TOF) analysis method for benzodiazepines in urine samples from alleged drug-facilitated sexual assault victims","volume":"30","author":"ElSohly","year":"2006","journal-title":"Journal of Analytical Toxicology"},{"key":"2022032114033123800_R10","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.kjms.2016.01.007","article-title":"Simultaneous identification of abused drugs, benzodiazepines, and new psychoactive substances in urine by liquid chromatography tandem mass spectrometry","volume":"32","author":"Lee","year":"2016","journal-title":"Kaohsiung Journal of Medical Sciences"},{"key":"2022032114033123800_R11","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/j.jpba.2011.06.007","article-title":"A fast liquid chromatography-tandem mass spectrometry method for determining benzodiazepines and analogues in urine. Validation and application to real cases of forensic interest","volume":"56","author":"Salomone","year":"2011","journal-title":"Journal of Pharmaceutical and Biomedical Analysis"},{"key":"2022032114033123800_R12","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/jat\/bks084","article-title":"Validation of LC-TOF-MS screening for drugs, metabolites, and collateral compounds in forensic toxicology specimens","volume":"37","author":"Guale","year":"2013","journal-title":"Journal of Analytical Toxicology"},{"key":"2022032114033123800_R13","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.jchromb.2016.05.010","article-title":"Rapid screening for drugs of abuse in biological fluids by ultra high performance liquid chromatography\/Orbitrap mass spectrometry","volume":"1027","author":"Jagerdeo","year":"2016","journal-title":"Journal of Chromatography B Analytical Technologies in the Biomedical and Life Sciences"},{"key":"2022032114033123800_R14","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1093\/jat\/bkv140","article-title":"Comparison of LC-MS-MS and GC-MS analysis of benzodiazepine compounds included in the drug demand reduction urinalysis program","volume":"40","author":"Perez","year":"2016","journal-title":"Journal of Analytical Toxicology"},{"key":"2022032114033123800_R15","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jchromb.2014.08.033","article-title":"Simultaneous detection of 93 conventional and emerging drugs of abuse and their metabolites in urine by UHPLC-MS\/MS","volume":"969","author":"Tang","year":"2014","journal-title":"Journal of Chromatography B Analytical Technologies in the Biomedical and Life Sciences"},{"key":"2022032114033123800_R16","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.chroma.2012.06.023","article-title":"The evaluation of the applicability of a high pH mobile phase in ultrahigh performance liquid chromatography tandem mass spectrometry analysis of benzodiazepines and benzodiazepine-like hypnotics in urine and blood","volume":"1249","author":"Verplaetse","year":"2012","journal-title":"Journal of Chromatography A"},{"key":"2022032114033123800_R17","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2020.105062","article-title":"Silica supported metal organic framework 808 composites as adsorbent for solid-phase extraction of benzodiazepines in urine sample","volume":"157","author":"Yang","year":"2020","journal-title":"Microchemical Journal"},{"key":"2022032114033123800_R18","doi-asserted-by":"crossref","first-page":"3924","DOI":"10.1039\/D0AY01025A","article-title":"A poly(N,N-dimethylaminoethyl methacrylate-co-ethylene glycol dimethacrylate) monolith for direct solid-phase extraction of benzodiazepines from undiluted human urine","volume":"12","author":"Zhao","year":"2020","journal-title":"Analytical Methods"},{"key":"2022032114033123800_R19","doi-asserted-by":"publisher","first-page":"6037","DOI":"10.1007\/s00216-020-02559-y.","article-title":"Twenty years of supramolecular solvents in sample preparation for chromatography: achievements and challenges ahead","volume":"412","author":"Rubio","year":"2020","journal-title":"Analytical and Bioanalytical Chemistry"},{"key":"2022032114033123800_R20","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s10337-018-3614-1.","article-title":"Hyphenating supramolecular solvents and liquid chromatography: tips for efficient extraction and reliable determination of organics","volume":"82","author":"Ballesteros-G\u00f3mez","year":"2019","journal-title":"Chromatographia"},{"key":"2022032114033123800_R21","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1021\/ac2026207","article-title":"Environment-responsive alkanol-based supramolecular solvents: characterization and potential as restricted access property and mixed-mode extractants","volume":"84","author":"Ballesteros-G\u00f3mez","year":"2012","journal-title":"Analytical Chemistry"},{"key":"2022032114033123800_R22","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1021\/acs.jafc.8b06003","article-title":"Restricted access volatile supramolecular solvents for single-step extraction\/cleanup of benzimidazole anthelmintic drugs in milk prior to LC-MS\/MS","volume":"67","author":"Accioni","year":"2019","journal-title":"Journal of Agricultural and Food Chemistry"},{"key":"2022032114033123800_R23","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.aca.2018.05.002.","article-title":"Speeding up the extraction of hexabromocyclododecane enantiomers in soils and sediments based on halogen bonding","volume":"1027","author":"Lara","year":"2018","journal-title":"Analytica Chimica Acta"},{"key":"2022032114033123800_R24","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.talanta.2018.02.039","article-title":"SUPRAS extraction approach for matrix-independent determination of amphetamine-type stimulants by LC-MS\/MS","volume":"182","author":"Accioni","year":"2018","journal-title":"Talanta"},{"key":"2022032114033123800_R25","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2020.461777","article-title":"Exploring polar hydrophobicity in organized media for extracting oligopeptides: application to the extraction of opiorphin in human saliva","volume":"1635","author":"Accioni","year":"2021","journal-title":"Journal of Chromatography A"},{"key":"2022032114033123800_R26","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.talanta.2015.11.014","article-title":"Restricted access supramolecular solvents for removal of matrix-induced ionization effects in mass spectrometry: application to the determination of Fusarium toxins in cereals","volume":"148","author":"Garc\u00eda-Fonseca","year":"2016","journal-title":"Talanta"},{"key":"2022032114033123800_R27","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.aca.2016.11.026","article-title":"The use of a restricted access volatile supramolecular solvent for the LC\/MS-MS assay of bisphenol A in urine with a significant reduction of phospholipid-based matrix effects","volume":"950","author":"Salatti-Dorado","year":"2017","journal-title":"Analytica Chimica Acta"},{"key":"2022032114033123800_R28","article-title":"Commission Decision of 12 August 2002 Implementing Council Directive 96\/23\/EC Concerning the Performance of Analytical Methods and the Interpretation of Results (Notified Under Document Number C(2002) 3044) \u2013 EU Monitor","author":"Decision 2002\/657-2002\/657\/EC"}],"container-title":["Journal of Analytical Toxicology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jat\/advance-article-pdf\/doi\/10.1093\/jat\/bkab023\/36549214\/bkab023.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jat\/article-pdf\/46\/3\/285\/42961785\/bkab023.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jat\/article-pdf\/46\/3\/285\/42961785\/bkab023.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T14:27:56Z","timestamp":1647872876000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jat\/article\/46\/3\/285\/6155037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,1]]},"references-count":28,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3,1]]},"published-print":{"date-parts":[[2022,3,21]]}},"URL":"https:\/\/doi.org\/10.1093\/jat\/bkab023","relation":{},"ISSN":["0146-4760","1945-2403"],"issn-type":[{"value":"0146-4760","type":"print"},{"value":"1945-2403","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,4,1]]},"published":{"date-parts":[[2021,3,1]]}}}