{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:13:29Z","timestamp":1753892009478,"version":"3.41.2"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>An UPLC-MS\/MS method was developed and validated for simultaneous determination of atracurium (ATC), dexmedetomidine (DEX), midazolam (MDZ) and 1-hydroxymidazolam (1-OH-MDZ) and the pharmacokinetics of ATC, DEX, MDZ and 1-OH-MDZ in patients undergoing aortic dissection surgery were investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The analytes were extracted by acetonitrile precipitation and separated on an Acquity UPLC BEH C18 column (2.1\u00a0mm \u00d7 50\u00a0mm, 1.7\u00a0\u03bcm) with a mobile phase of acetonitrile-0.1% formic acid and a gradient mode. In the positive ion mode, the following mass transition pairs were monitored by multiple reaction monitoring (MRM) for the four analytes and IS: m\/z 385.1\u2192206.2 for ATC, m\/z 201.2\u219295.1 for DEX, m\/z 326.1\u2192291.1 for MDZ, m\/z 341.9\u2192324.0 for 1-OH-MDZ, and 284.9\u2192153.9 for diazepam (IS). Seven male patients undergoing aortic dissection surgery received general anesthesia and intravenous administration of ATC, DEX, and MDZ during the surgery. Venous blood was collected at different time points at the end of surgery and after surgery. The concentrations of ATC, DEX, MDZ, and 1-OH-MDZ were detected, and the pharmacokinetic parameters were calculated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The method showed good linearity for each analyte. The inter-batch precision ranged from 1.37% to 9.87% and the intra-batch precision ranged from 2.41% to 10.72%; the accuracy ranged from 94.33% to 104.51%. Finally, the matrix effect, extraction recovery and stability data met the FDA recommended acceptance criteria for validation of bioanalytical methods. The t<jats:sub>1\/2<\/jats:sub> of ATC, DEX, MDZ and 1-OH-MDZ was (6.74 \u00b1 2.27) h, (9.55 \u00b1 4.93) h, (10.17 \u00b1 5.35) h, and (6.90 \u00b1 2.38) h, the C<jats:sub>max<\/jats:sub>, of ATC, DEX, MDZ and 1-OH-MDZ was (1054.20 \u00b1 202.37) ng\/mL, (1.93 \u00b1 1.07) ng\/mL, (1256.57 \u00b1 389.09) ng\/mL, and (1034.39 \u00b1 292.92) ng\/mL in patients undergoing aortic dissection surgery, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The developed UPLC-MS\/MS method for simultaneous determination of ATC, DEX, MDZ and 1-OH-MDZ in patient plasma was accurate, reproducible, specific. After continuous administration of ATC, DEX, and MDZ to patients undergoing surgery for acute aortic dissection, the pharmacokinetics of ATC, DEX, MDZ and 1-OH-MDZ in patients undergoing aortic dissection surgery were studied.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1427553","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T04:53:58Z","timestamp":1729745638000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics study of atracurium, dexmedetomidine, midazolam and 1-hydroxymidazolam in patients undergoing acute aortic dissection surgery"],"prefix":"10.3389","volume":"15","author":[{"given":"Huiling","family":"Si","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuanxuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhao","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuaibo","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1093\/bja\/65.5.668","article-title":"Pharmacokinetics of atracurium during continuous infusion","volume":"65","author":"Beemer","year":"1990","journal-title":"Br. J. Anaesth."},{"key":"B2","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1111\/j.1600-0773.1993.tb01551.x","article-title":"Inhibition of hepatic microsomal drug metabolism by atracurium administration in the rat","volume":"73","author":"B\u00f6hrer","year":"1993","journal-title":"Pharmacol. Toxicol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1177\/87551225231194031","article-title":"Atracurium versus cisatracurium in the treatment of acute respiratory distress syndrome","volume":"39","author":"Carabetta","year":"2023","journal-title":"J. Pharm. Technol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"37","DOI":"10.4103\/joacp.JOACP_36_19","article-title":"Determination of dose and efficacy of atracurium for rapid sequence induction of anesthesia: a randomised prospective study","volume":"36","author":"Chalermkitpanit","year":"2020","journal-title":"J. Anaesthesiol. Clin. Pharmacol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"63","DOI":"10.3867\/j.issn.1000-3002.2019.01.009","article-title":"Pharmacokinetics and sedation of sufentanil and dexmedetomidine combination in rats","volume":"33","author":"Chang","year":"2019","journal-title":"Chin. J. Pharmacol. Toxicol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.2147\/DDDT.S405294","article-title":"Dexmedetomidine as an adjuvant in peripheral nerve block","volume":"17","author":"Chen","year":"2023","journal-title":"Drug Des. Devel Ther."},{"key":"B7","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1213\/ANE.0000000000006487","article-title":"Dexmedetomidine pretreatment protects against myocardial ischemia\/reperfusion injury by activating STAT3 signaling","volume":"137","author":"Chen","year":"2023","journal-title":"Anesth. Analg."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1021\/acs.biochem.1c00161","article-title":"Midazolam as a probe for drug-drug interactions mediated by CYP3A4: homotropic allosteric mechanism of site-specific hydroxylation","volume":"60","author":"Denisov","year":"2021","journal-title":"Biochemistry"},{"key":"B9","doi-asserted-by":"publisher","first-page":"853","DOI":"10.3390\/biom12060853","article-title":"Midazolam as a probe for heterotropic drug-drug interactions mediated by CYP3A4","volume":"12","author":"Denisov","year":"2022","journal-title":"Biomolecules"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2873","DOI":"10.1093\/eurheartj\/ehu281","article-title":"2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC)","volume":"35","author":"Erbel","year":"2014","journal-title":"Eur. Heart J."},{"key":"B11","doi-asserted-by":"publisher","first-page":"849","DOI":"10.4103\/ija.ija_285_22","article-title":"Comparison of different doses of atracurium for quality of muscle relaxation during modified rapid sequence induction in emergency laparotomy: a prospective randomised double blind study","volume":"66","author":"Holkunde","year":"2022","journal-title":"Indian J. Anaesth."},{"key":"B12","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1186\/s13019-023-02300-7","article-title":"Dexmedetomidine ameliorates diabetic cardiomyopathy by inhibiting ferroptosis through the Nrf2\/GPX4 pathway","volume":"18","author":"Li","year":"2023","journal-title":"J. Cardiothorac. Surg."},{"volume-title":"Midazolam: StatPearls","year":"2023","author":"Lingamchetty","key":"B13"},{"volume-title":"LiverTox: clinical and research information on drug-induced liver injury","year":"2023","key":"B14"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e84","DOI":"10.1136\/bmjspcare-2020-002334","article-title":"Dexmedetomidine for dyspnoea","volume":"13","author":"Mano","year":"2023","journal-title":"BMJ Support Palliat. Care"},{"volume-title":"Atracurium: StatPearls","year":"2023","author":"Ritz","key":"B16"},{"key":"B17","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1093\/eurheartj\/ehac757","article-title":"Acute aortic dissection: evidence, uncertainties, and future therapies","volume":"44","author":"Rylski","year":"2023","journal-title":"Eur. Heart J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"28","DOI":"10.4103\/abr.abr_61_19","article-title":"Comparing the safety and efficacy of three different doses of atracurium in facilitating the insertion of laryngeal mask airway in patients undergoing phacoemulsification cataract surgery: a randomized clinical trial","volume":"9","author":"Shetabi","year":"2020","journal-title":"Adv. Biomed. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.anclin.2022.08.012","article-title":"Aortic dissection","volume":"40","author":"Stombaugh","year":"2022","journal-title":"Anesthesiol. Clin."},{"key":"B20","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1007\/s00540-023-03261-w","article-title":"Dexmedetomidine as acardioprotective drug: a narrative review","volume":"37","author":"Takahashi","year":"2023","journal-title":"J. Anesth."},{"key":"B21","doi-asserted-by":"publisher","first-page":"122249","DOI":"10.1016\/j.lfs.2023.122249","article-title":"Epigenomics in aortic dissection: from mechanism to therapeutics","volume":"335","author":"Tao","year":"2023","journal-title":"Life Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1150135","DOI":"10.3389\/fneur.2023.1150135","article-title":"Anesthesia, the developing brain, and dexmedetomidine for neuroprotection","volume":"14","author":"Tsivitis","year":"2023","journal-title":"Front. Neurol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.xjtc.2020.03.012","article-title":"A simple method to establish antegrade cerebral perfusion during hemiarch reconstruction","volume":"2","author":"Wai Sang","year":"2020","journal-title":"JTCVS Tech."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e2318611","DOI":"10.1001\/jamanetworkopen.2023.18611","article-title":"Effect of dexmedetomidine on posttraumatic stress disorder in patients undergoing emergency trauma surgery: a randomized clinical trial","volume":"6","author":"Yu","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"B25","doi-asserted-by":"publisher","first-page":"2595","DOI":"10.2147\/DDDT.S254055","article-title":"Effects of dexmedetomidine on the pharmacokinetics of dezocine, midazolam and its metabolite 1-hydroxymidazolam in beagles by UPLC-MS\/MS","volume":"14","author":"Zhou","year":"2020","journal-title":"Drug Des. Devel Ther."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1427553\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T04:54:02Z","timestamp":1729745642000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1427553\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,24]]},"references-count":25,"alternative-id":["10.3389\/fphar.2024.1427553"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1427553","relation":{},"ISSN":["1663-9812"],"issn-type":[{"type":"electronic","value":"1663-9812"}],"subject":[],"published":{"date-parts":[[2024,10,24]]},"article-number":"1427553"}}