title: Determination of artemisitene in rat plasma by ultra-performance liquid chromatography/tandem mass spectrometry and its application in pharmacokinetics.
abstract: BACKGROUND
  Artemisitene shows a wide variety of pharmacological activities, such as antioxidant protection in vitro and in vivo. It has been identified as a novel Nrf2 inducer. However, there is no report on an ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method to quantitate artemisitene in rat plasma and its application to a pharmacokinetic profile study.
  
  
  METHODS
  An ACQUITY UPLC™ BEH Symmetry Shield RP18 column (1.7 μm, 2.1 mm × 100 mm) was used at a flow rate of 0.3 mL·min-1. Mass detection was performed by electrospray ionization tandem mass spectrometry via multiple reaction monitoring (MRM) in positive mode. Plasma samples were pre-treated by a single-step extraction with 0.1% formic acid aqueous solutions-acetonitrile, and tolbutamide was used as internal standard.
  
  
  RESULTS
  The calibration curve was from 0.98 to 1000 ng∙mL-1(r2= 0.995). The extraction recoveries were 61.5-79.4% and 81.7-94.6% for artemisitene and tolbutamide, respectively. The lower limit of quantification (LLOQ) was 0.98 ng∙mL-1. The absolute bioavailability of artemisitene was 3.7% after intravenous and oral administration in rats.
  
  
  CONCLUSIONS
  The UPLC/MS/MS assay was validated for linearity, accuracy, stability, extraction recovery, matrix effects, and intra-day and inter-day precision. The method, for the first time, achieved some pharmacokinetic parameters and was successfully applied to a pharmacokinetic study Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: The Second Clinical College, Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, P.R. China.
authors.forename: Li-Lan
authors.initials: LL
authors.lastname: Wu
authors.affiliation: The Second Clinical College, Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, P.R. China.
authors.forename: Yun-Shan
authors.initials: YS
authors.lastname: Wu
authors.affiliation: The Second Clinical College, Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, P.R. China.
authors.forename: Wei-Ying
authors.initials: WY
authors.lastname: Chen
authors.affiliation: The Second Clinical College, Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhou
authors.affiliation: The Second Clinical College, Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, P.R. China.
authors.forename: Lipeng
authors.initials: L
authors.lastname: Tang
authors.affiliation: The Second Clinical College, Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, P.R. China.
authors.forename: Ben
authors.initials: B
authors.lastname: Li
authors.affiliation: The Second Clinical College, Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, P.R. China.
authors.forename: Bo
authors.identifier: http://orcid.org/0000-0002-9539-2005
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D037621:Artemisinins; C105118:artemisitene