{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:53:02Z","timestamp":1791186782373,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2026,12,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Stable isotope\u2010labeled compounds are indispensable internal standards for reliable liquid chromatography\u2013mass spectrometry (LC\u2010MS) analysis, but their preparation frequently requires multistep synthesis. Base\u2010catalyzed hydrogen\u2013deuterium exchange at carbon centers provides a simple alternative for generating stable isotopologues. Beyond quantitative applications, carbon\u2010bound deuterium may serve as a mechanistic probe for investigating gas\u2010phase fragmentation and chemically induced molecular transformations. In this work, tadalafil and omeprazole were selected as complementary model compounds to evaluate both the analytical applicability of deuterium\u2010labeled standards and the behavior of carbon\u2010bound deuterium during tandem mass spectrometry and acid\u2010induced transformation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Deuterium\u2010labeled tadalafil and omeprazole were prepared by base\u2010catalyzed hydrogen\u2013deuterium exchange under optimized reaction conditions. The obtained isotopologue mixtures were characterized using high\u2010resolution ESI\u2010MS, multistage tandem mass spectrometry,\n                      <jats:sup>1<\/jats:sup>\n                      H NMR spectroscopy, and density functional theory (DFT) calculations. Their chromatographic behavior, short\u2010term isotope stability, and proof\u2010of\u2010concept applicability as LC\u2010MS internal standards were evaluated using chromatographic comparison and analysis of post\u2010dose human urine samples.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Base\u2010catalyzed hydrogen\u2013deuterium exchange produced isotopologue mixtures dominated by tadalafil\u2010d\n                      <jats:sub>3<\/jats:sub>\n                      and omeprazole\u2010d\n                      <jats:sub>2<\/jats:sub>\n                      . High\u2010resolution mass spectrometry and\n                      <jats:sup>1<\/jats:sup>\n                      H NMR spectroscopy consistently identified selective incorporation of carbon\u2010bound deuterium, whereas DFT calculations explained the observed regioselectivity of the exchange. Tandem mass spectrometry of deuterated tadalafil revealed product\u2010ion mass shifts consistent with hydrogen scrambling, demonstrating migration of carbon\u2010bound deuterium during collision\u2010induced dissociation and providing additional insight into the dissociation mechanism. In contrast, deuterium\u2010labeled omeprazole retained its isotope label during acid\u2010induced transformation. Both labeled compounds exhibited chromatographic behavior suitable for proof\u2010of\u2010concept LC\u2010MS applications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Base\u2010catalyzed carbon hydrogen\u2013deuterium exchange provides a rapid and cost\u2010effective approach for preparing stable isotope\u2010labeled tadalafil and omeprazole suitable for LC\u2010MS applications. The study further demonstrates that carbon\u2010bound deuterium constitutes a valuable mechanistic probe, enabling investigation of hydrogen scrambling during tandem mass spectrometry and evaluation of isotope\u2010label stability during acid\u2010induced molecular transformation. The combined HRMS, tandem MS, NMR, and DFT approach establishes a comprehensive framework for characterization of deuterium\u2010labeled compounds and supports their future application in quantitative analysis as well as structural elucidation by mass spectrometry.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.70188","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:17:58Z","timestamp":1790057878000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preparation of Deuterium\u2010Labeled Tadalafil and Omeprazole by Carbon Hydrogen\u2013Deuterium Exchange: Hydrogen Scrambling, Acid\u2010Induced Transformation, and LC\u2010MS Applications"],"prefix":"10.1002","volume":"40","author":[{"given":"Martyna","family":"Hofman\u2010Kotyla","sequence":"first","affiliation":[{"name":"Faculty of Chemistry University of Wroclaw  Wroc\u0142aw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Grocholska\u2010Zamiara","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry University of Wroclaw  Wroc\u0142aw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Wieczorek","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry University of Wroclaw  Wroc\u0142aw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1247-8709","authenticated-orcid":false,"given":"Remigiusz","family":"B\u0105chor","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry University of Wroclaw  Wroc\u0142aw 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