HPLC - MS / MS Determination of Fraxetin in Rat Plasma and its Application to a Pharmacokinetic Study

Background: Fraxetin is mainly an active ingredient of Fraxini Cortex which is an important and traditional Chinese medicine for clinical applications, has heat-clearing, dispelling dampness, anti-tussive and anti-asthmatic effects. Fraxetin has a variety of pharmacological activities. Method: The chromatographic separation was carried out on a Zorbax Eclipse XDB C18 column. The mobile phase consisted of acetonitrile (0.1 % formic acid) and ammonium acetate (0.1 % formic acid). Samples were prepared with protein precipitation. Result: The method had good linearity within 10 - 2500 ng/mL. Both intra- and inter-assay precisions were acceptable and <= 8.5 %. Extraction recovery was 75.9 - 89.5 %, and the lower limit of quantification for fraxetin was 10 ng/mL. This proposed method was successfully used to study the pharmacokinetic and bioavailability of fraxetin after 5 and 25 mg/kg fraxetin were administered to rats via intravenous and oral routes, respectively. The half-life (t(1/2)) of fraxetin for i.v was (3.86 +/- 0.65) h. The t(1/2) of fraxetin for p.o was (4.41 +/- 1.79) h. The bioavailability of fraxetin is 12.6%. Conclusion: The results provided some useful information for the future development and clinical medication of fraxetin.