{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:48:05Z","timestamp":1788878885811,"version":"build-2803163510"},"reference-count":18,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"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":["Biomedical Chromatography"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Etomidate and its structural analogs\u2014metomidate, propoxate, and isopropoxate\u2014have emerged as prevalent substances of abuse in China due to their high addictive potential. This study developed and validated a sensitive, reliable, and high\u2010throughput method using HPLC\u2013MS\/MS for simultaneous quantification of four imidazoline\u2010derived new psychoactive substances and the metabolite etomidate acid and then applied it for the molecular pharmacokinetics of five analytes in murine blood. Method validation demonstrated excellent linearity (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u2009\u2265\u20090.999) across calibration curves, with LLOQ ranging from 0.2 to 1\u2009ng\/mL and LOD ranging from 0.1 to 0.5\u2009ng\/mL. Intraday\/interday precision reached 0.123%\u201311.2%, and accuracy was in the range of \u22129.68% to 9.86%, which met bioanalytical criteria. Recovery rates (89.3%\u2013103%) and matrix effects (87.1%\u2013105%) were within acceptable ranges. Male KM mice with a body weight of 25\u2009\u00b1\u20092\u2009g were selected for pharmacokinetic evaluation. Pharmacokinetic analysis revealed significant dose\u2010dependent relationships for maximum plasma concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>), area under the concentration\u2013time curve (AUC<jats:sub>0\u2013\u221e<\/jats:sub>), and detection window (<jats:italic>T<\/jats:italic><jats:sub>window<\/jats:sub>). Metabolic rates followed a descending order: propoxate\u2009&gt;\u2009isopropoxate\u2009&gt;\u2009etomidate\u2009&gt;\u2009metomidate, likely attributed to their lipophilicity gradient. This study systematically elucidates the dose\u2010metabolism kinetics and structure\u2013activity relationships of etomidate analogs, addressing the knowledge gap in toxicokinetic data for propoxate and isopropoxate.<\/jats:p>","DOI":"10.1002\/bmc.70226","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T02:40:05Z","timestamp":1759113605000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Simple and Sensitive HPLC\u2013MS\/MS Method for the Simultaneous Quantitative Analysis and Pharmacokinetic Comparison of Four Imidazole\u2010Derived GABA Receptor Agonists: Etomidate, Metomidate, Propoxate, and Isopropoxate in Mouse Blood"],"prefix":"10.1002","volume":"39","author":[{"given":"Yuxuan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Legal Medicine, College of Basic Medical Sciences Inner Mongolia Medical University  Hohhot 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