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