{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T10:26:14Z","timestamp":1774434374958,"version":"3.50.1"},"reference-count":63,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"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":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2026,2,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>This study presents a novel LC\u2010MS approach for the determination of ethyl glucuronide (EtG), an important alcohol biomarker, in biosamples following derivatization with N\u2010(3\u2010dimethylaminopropyl)\u2010N\u2032\u2010ethylcarbodiimide (EDC). This addresses several drawbacks of previously published LC\u2010MS methods for EtG, including poor chromatographic performance with reversed\u2010phase columns and unfavorable ionization in positive ESI mode, necessitating negative ESI conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The EtG and D\n                      <jats:sub>5<\/jats:sub>\n                      \u2010EtG derivatization procedure involves reacting with 10\u2010mM aqueous EDC at 25\u00b0C for 30\u2009min. The derivatives were structurally characterized by LC\u2010HRAM\u2010Orbitrap\u2010MS through the evaluation of their chromatographic behavior, accurate mass measurements of their MH\n                      <jats:sup>+<\/jats:sup>\n                      ions, evaluation of their characteristic MH\n                      <jats:sup>+<\/jats:sup>\n                      isotopic patterns, and accurate mass measurements of MH\n                      <jats:sup>+<\/jats:sup>\n                      collision\u2010induced product ions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Derivatization produces two EtG\u2010EDC derivatives characterized by the same exact mass (MH\n                      <jats:sup>+<\/jats:sup>\n                      at\n                      <jats:italic>m\/z<\/jats:italic>\n                      378.2235) and elemental composition (C\n                      <jats:sub>16<\/jats:sub>\n                      H\n                      <jats:sub>31<\/jats:sub>\n                      N\n                      <jats:sub>3<\/jats:sub>\n                      O\n                      <jats:sub>7<\/jats:sub>\n                      ) but different molecular structures (EtG\u2010EDC\n                      <jats:sub>A<\/jats:sub>\n                      and EtG\u2010EDC\n                      <jats:sub>B<\/jats:sub>\n                      ). Equivalent results were obtained for D\n                      <jats:sub>5<\/jats:sub>\n                      \u2010EtG: production of two deuterated N\u2010acylureas with MH\n                      <jats:sup>+<\/jats:sup>\n                      ions at\n                      <jats:italic>m\/z<\/jats:italic>\n                      383.2349, elemental composition C\n                      <jats:sub>16<\/jats:sub>\n                      H\n                      <jats:sub>26<\/jats:sub>\n                      D\n                      <jats:sub>5<\/jats:sub>\n                      N\n                      <jats:sub>3<\/jats:sub>\n                      O\n                      <jats:sub>7<\/jats:sub>\n                      , and different molecular structures (D\n                      <jats:sub>5<\/jats:sub>\n                      \u2010EtG\u2010EDC\n                      <jats:sub>A<\/jats:sub>\n                      and D\n                      <jats:sub>5<\/jats:sub>\n                      \u2010EtG\u2010EDC\n                      <jats:sub>B<\/jats:sub>\n                      ). Derivatization completely modifies the chemical properties of EtG and D\n                      <jats:sub>5<\/jats:sub>\n                      \u2010EtG, increasing the molecular weight by 155 u, and introducing three nitrogen atoms. The derivatives remained stable for at least 15\u2009days, even at room temperature. Three preliminary analytical methods for the determination of EtG in urine, blood, and hair samples, were developed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>EtG\u2010EDC derivatives demonstrate efficient chromatographic performance on reversed\u2010phase LC columns and undergo protonation easily in the MS ion source, enabling MS detection under positive ionization conditions. The derivatization is simple, fast, reproducible, inexpensive, and safe, as it is obtained in 30\u2009min at low temperatures, starting from a commercially available carbodiimide, without organic solvents and catalyzing agents. This analytical strategy offers a novel approach to detect EtG in biosamples by combining the benefits of chemical derivatization and high\u2010resolution mass spectrometry.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.70000","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T05:26:04Z","timestamp":1764566764000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ethyl Glucuronide (EtG) Derivatization With N\u2010(3\u2010Dimethylaminopropyl)\u2010N\u2032\u2010Ethylcarbodiimide (EDC). LC\u2010HRAM\u2010Orbitrap\u2010MS Characterization of Derivatives and Application to Blood, Urine, and Hair Analysis"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6545-4109","authenticated-orcid":false,"given":"Giampietro","family":"Frison","sequence":"first","affiliation":[{"name":"Laboratory of Clinical and Forensic Toxicology, DMPO Department AULSS 3  Venice Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilisa","family":"Coppo","sequence":"additional","affiliation":[{"name":"Department of Life Sciences University of Trieste  Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7916-5216","authenticated-orcid":false,"given":"Flavio","family":"Zancanaro","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Forensic Toxicology, DMPO Department AULSS 3  Venice 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