Determination of ginsenosides Rb1, Rb2, and Rb3 in rat plasma by a rapid and sensitive liquid chromatography tandem mass spectrometry method: Application in a pharmacokinetic study

A sensitive rapid resolution liquid chromatography-tandem mass spectrometry method was developed to determine the pharmacokinetics of ginsenoside Rb(1), Rb(2), and Rb(3) in rats, after oral administration (50mg/kg) and intravenous administration (10mg/kg) of Rb(1), Rb(2), and Rb(3), respectively. The plasma samples were extracted by saturated N-butanol with Rg(2) as internal standard. Chromatographic separation was performed on a Zorbax SB-C18 column (50 mm × 4.6 mm, 1.8 μm) with a mobile phase consisting of methanol and 1mM ammonium formate (74:26, v/v). Multiple reaction monitoring mode was performed using the fragmentation transitions of m/z 1107.7→m/z 178.9, m/z 1077.7→m/z 148.6, and m/z 1077.7→m/z 783.4 for Rb(1), Rb(2), and Rb(3), respectively. Calibration curves were recovered over a concentration range of 20-1000 ng/ml for Rb(1) and Rb(2), and 50-2500 ng/ml for Rb(3). The limits of detection were 3.0 ng/ml, 4.0 ng/ml, and 6.5 ng/ml. Both intra-day and inter-day variances were less than 15% and the accuracy was within 86-114% for the three ginsenosides. All three ginsenosides had poor oral bioavailability (0.78%, 0.08%, and 0.52% for Rb(1), Rb(2), and Rb(3), respectively). The value of Rb(1) is higher than that of Rb(2) or Rb(3), indicating that ginsenosides with hexose and hydroxyl groups (Rb(1)) could present better pharmacokinetic behaviors than those with pentose groups in the same glycosylation site by oral administration.