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Journal of Chinese Pharmaceutical Sciences ›› 2017, Vol. 26 ›› Issue (10): 747-753.DOI: 10.5246/jcps.2017.10.084

• Original articles • Previous Articles     Next Articles

Determination of 8,2′-diprenylquercetin 3-methyl ether in plasma by UPLC-MS-MS and its pharmacokinetic application in rats

Huan Liu, Shanshan Fan, Wen Zhang, Yifan Zhang, Teng Li, Mingying Shang*, Guangxue Liu, Feng Xu, Shaoqing Cai   

  1. Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2017-08-27 Revised:2017-09-25 Online:2017-10-31 Published:2017-10-12
  • Contact: Tel.: +86-010-82802534, E-mail: myshang@bjmu.edu.cn
  • Supported by:

    National Natural Science Foundation of China (Grant No. 81673590) and National Key Technology R&D Program “New Drug Innovation” of China (Grant No. 2013ZX09103002-006).

Abstract:

8,2′-Diprenylquercetin 3-methyl ether with significant anti-breast cancer activityis the main constituent of Tibetan medicine Sinopodophylli Fructus. In the present study, we developed and validated a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of 8,2′-diprenylquercetin 3-methyl etherin rat plasma. 8-Prenylkaempferol was used as the internal standard. The separation was carried out using Waters ACQUITY UPLC BEH C18 column (2.1 mm×100 mm, 1.7 µm) with a mobile phase consisting of acetonitrile and 0.1% formic acid in water on a gradient program at a flow rate of 0.4 mL·min–1 and temperature of 30 ºC. Triple quadrupole mass spectrometric detection in negative ion mode was used for multiple-reaction monitoring of the transitions at m/z 451.30→177.25 and m/z 353.25→298.15 for 8,2′-diprenylquercetin 3-methyl ether and 8-prenylkaempferol, respectively. The calibration curves were linear within the concentration range 0.1–2000 ng/mL (r = 0.9954). The recoveries were 103%–115%, and the results were consistent across low, middle and high concentration levels. The intra- and inter-day precisions were within 15%, and the bias was between –6%~15%. This method was simple, rapid and sensitive, which could be applied to the determination of 8,2′-diprenylquercetin 3-methyl ether in plasma and pharmacokinetic study in rats. Pharmacokinetic test indicated that the peak plasma concentration occurred in 2 h after the female rats were intragastrically administered with 8,2′-diprenylquercetin 3-methyl ether at the dose of 100 mg/kg, and the biological half-life was 6.79 h. The blood drug concentration maintained equal amount for 20 h, which was conducive to the in vivo effects of drugs.

Key words: 8,2'-Diprenylquercetin 3-methyl ether, UPLC-MS/MS, Blood concentration, Anti-breast cancer, Pharmacokinetic

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