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 Rb1, Rb2, and Rb3 in rats, after oral administration (50 mg/kg) and intravenous administration (10 mg/kg) of Rb1, Rb2, and Rb3, respectively. The plasma samples were extracted by saturated N-butanol with Rg2 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 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 Rb1, Rb2, and Rb3, respectively. Calibration curves were recovered over a concentration range of 20–1000 ng/ml for Rb1 and Rb2, 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 Rb1, Rb2, and Rb3, respectively). The value of Rb1 is higher than that of Rb2 or Rb3, indicating that ginsenosides with hexose and hydroxyl groups (Rb1) could present better pharmacokinetic behaviors than those with pentose groups in the same glycosylation site by oral administration.