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 (50 mg/kg) and intravenous administration (10 mg/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 x 4.6 mm, 1.8 mu m) with a mobile phase consisting of methanol and 1 mM 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 Rb3. 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. (C) 2012 Elsevier B.V. All rights reserved.