{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T11:38:52Z","timestamp":1771328332945,"version":"3.50.1"},"reference-count":19,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2015,4,16]],"date-time":"2015-04-16T00:00:00Z","timestamp":1429142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In order to investigate the pharmacokinetics of a combination of diazepam and dexamethasone under hypoxic conditions, a novel, sensitive and specific liquid chromatography with tandem mass spectrometry (LC-MS\/MS) method for the simultaneous determination of diazepam and dexamethasone in rat plasma was developed and validated. The chromatographic separation of analytes was successfully achieved on an XTerra\u00ae MS C18 column using a gradient elution of methanol and water containing 0.1% formic acid at a flow rate of 0.5 mL\/min. This method demonstrated good linearity and no endogenous material interferences. The linear ranges were 1.0\u2013100 ng\/mL for diazepam and 2.0\u2013200 ng\/mL for dexamethasone. The intra- and inter-day precision for the two compounds in plasma were lower than 10.0%, and the accuracy was between \u22127.9% and 11.5%. Our method was then successfully applied in a pharmacokinetic comparison between normoxic and hypoxic rats. The results indicated that there were significant differences in the main pharmacokinetics parameters of diazepam and dexamethasone between normoxic and hypoxic rats. The results provide the important and valuable information for discovering and developing novel anti-hypoxia drug combinations, as well as a better understanding of the safety and efficacy of these drugs.<\/jats:p>","DOI":"10.3390\/molecules20046901","type":"journal-article","created":{"date-parts":[[2015,4,16]],"date-time":"2015-04-16T10:37:57Z","timestamp":1429180677000},"page":"6901-6912","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Simultaneous Quantification of Diazepam and Dexamethasone  in Plasma by High-Performance Liquid Chromatography with Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Comparison between Normoxic and  Hypoxic Rats"],"prefix":"10.3390","volume":"20","author":[{"given":"Wenwen","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University,  Beijing 100069, China"},{"name":"Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cognitive Sciences, Beijing Institute of Basic Medical Sciences, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pingxiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China"},{"name":"Beijing Laboratory for Biomedical Detection Technology and Instrument,  Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University,  Beijing 100069, China"},{"name":"Department of Cognitive Sciences, Beijing Institute of Basic Medical Sciences, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China"},{"name":"Beijing Laboratory for Biomedical Detection Technology and Instrument,  Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1089\/ham.2009.1004","article-title":"Effect of six days of staging on physiologic adjustments and acute mountain sickness during ascent to 4300 meters","volume":"10","author":"Beidleman","year":"2009","journal-title":"High Alt. Med. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1056\/NEJM200107123450206","article-title":"High-altitude illness","volume":"345","author":"Hackett","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"257","DOI":"10.2174\/1389200043335577","article-title":"Effect of hypoxia on cytochrome P450 activity and expression","volume":"5","author":"Fradette","year":"2004","journal-title":"Curr. Drug Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jns.2007.05.019","article-title":"Acute mountain sickness with reversible vasospasm","volume":"263","author":"Johmura","year":"2007","journal-title":"J. Neurol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1580\/0953-9859-5.1.34","article-title":"Acetazolamide or dexamethasone for prevention of acute mountain sickness: A meta-analysis","volume":"5","author":"Douglas","year":"1994","journal-title":"J. Wilderness Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"283","DOI":"10.2165\/00003088-199325040-00004","article-title":"Hypoxia, arterial pH and theophylline disposition","volume":"25","author":"Richer","year":"1993","journal-title":"Clin. Pharmacokinet."},{"key":"ref_7","first-page":"166","article-title":"Preventive effect of Gaoyuankang Capsule on acute high altitude diseases in mass troops landed at high altitude areas rapidly","volume":"27","author":"Zheng","year":"2005","journal-title":"Acta Acad. Med. Mil. Tertiae"},{"key":"ref_8","first-page":"6","article-title":"The anti-oxidation and anti-hypoxia effects of gaoyuankang on prevention of acute high altitude disease","volume":"15","author":"Li","year":"2005","journal-title":"J. High Alt. Med."},{"key":"ref_9","first-page":"394","article-title":"Antagonistic effects of aminophylline on air way inflammation and oxidative lung tissue damage in chronic hypoxic rats","volume":"21","author":"Zhang","year":"2005","journal-title":"Chin. J. Pathophysiol."},{"key":"ref_10","first-page":"62","article-title":"Anti-hypoxia and anti-oxidation effects of aminophylline on huaman with acute high-altitude exposure","volume":"22","author":"Yang","year":"2007","journal-title":"Chin. Med. Sci. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.jpba.2006.06.042","article-title":"High throughput HPLC-ESI-MS method for the quantitation of dexamethasone in blood plasma","volume":"43","author":"Damonte","year":"2007","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1152\/japplphysiol.01414.2012","article-title":"Dexamethasone mimics aspects of physiological acclimatization to 8 h of hypoxia but suppresses plasma erythropoietin","volume":"114","author":"Liu","year":"2013","journal-title":"J. Appl. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"480","DOI":"10.3390\/molecules17010480","article-title":"A pampa assay as fast predictive model of passive human skin permeability of new synthesized corticosteroid c-21 esters","volume":"17","author":"Markovic","year":"2012","journal-title":"Molecules"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"659","DOI":"10.2298\/VSP0710659D","article-title":"Determination of diazepam and its metabolites in serum by the use of liquid chromatography\u2014Mass spectrometry method","volume":"64","author":"Dordevic","year":"2007","journal-title":"Vojnosanit. Pregl."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1002\/rcm.3613","article-title":"Determination of diazepam and its metabolites in human urine by liquid chromatography\/tandem mass spectrometry using a hydrophilic polymer column","volume":"22","author":"Umezawa","year":"2008","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/bmc.788","article-title":"Quantification of dexamethasone and corticosterone in rat biofluids and fetal tissue using highly sensitive analytical methods: assay validation and application to a pharmacokinetic study","volume":"21","author":"Samtani","year":"2007","journal-title":"Biomed. Chromatogr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jchromb.2007.09.003","article-title":"Simultaneous determination of cortisol, dexamethasone, methylprednisolone, prednisone, prednisolone, mycophenolic acid and mycophenolic acid glucuronide in human plasma utilizing liquid chromatography\u2013tandem mass spectrometry","volume":"859","author":"DiFrancesco","year":"2007","journal-title":"J. Chromatogr. B"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jchromb.2007.11.033","article-title":"Simultaneous quantitation of dexamethasone palmitate and dexamethasone in human plasma by liquid chromatography\/tandem mass spectrometry","volume":"862","author":"Yang","year":"2008","journal-title":"J. Chromatogr. B"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12065","DOI":"10.3390\/molecules190812065","article-title":"Comparative pharmacokinetics study of sinomenine in rats after oral administration of sinomenine monomer and Sinomenium acutum extract","volume":"19","author":"Zhang","year":"2014","journal-title":"Molecules"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/20\/4\/6901\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:44:51Z","timestamp":1760215491000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/20\/4\/6901"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,16]]},"references-count":19,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,4]]}},"alternative-id":["molecules20046901"],"URL":"https:\/\/doi.org\/10.3390\/molecules20046901","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,16]]}}}