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.
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® 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 1.0-100 ng/mL for diazepam and 2.0-200 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 -7.9% 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.
Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. syxpx88@163.com.|Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. syxpx88@163.com.
Wenwen
W
Gong
Department of Cognitive Sciences, Beijing Institute of Basic Medical Sciences, Beijing 100850, China. riever62002@126.com.
Shuhong
S
Liu
Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. syxpx88@163.com.|Beijing Laboratory for Biomedical Detection Technology and Instrument, Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. syxpx88@163.com.
Pingxiang
P
Xu
Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. fanmingchina@126.com.|Department of Cognitive Sciences, Beijing Institute of Basic Medical Sciences, Beijing 100850, China. fanmingchina@126.com.
Ming
M
Fan
Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. xuem@ccmu.edu.cn.|Beijing Laboratory for Biomedical Detection Technology and Instrument, Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. xuem@ccmu.edu.cn.
Ming
M
Xue
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003907:Dexamethasone / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003975:Diazepam / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000860:Hypoxia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods
D003907:Dexamethasone; D003975:Diazepam