Pharmacokinetics of Isorhynchophylline in Rat Plasma after Intravenous Administration

Isorhynchophylline is the main tetracycline hydroxindole alkaloid in uncaria, which has similar pharmacological activity with uncaria. In this study, we used UPLC-MS/MS to detect isorhynchophylline in rat plasma, and investigated its pharmacokinetics in rats. Diazepam was utilized as an internal standard (IS), and acetonitrile precipitation method was used to process the plasma samples. Chromatographic separation was achieved using a UPLC BEH C18 column using mobile phase of acetonitrile:0.1 % formic acid with gradient elution. Electrospray ionization (ESI) tandem mass spectrometry in multiple reaction monitoring (MRM) mode with positive ionization was applied. The results indicated that within the range of 1-200 ng/mL, linearity of isorhynchophylline in rat plasma was acceptable (r > 0.995), and the lower limit of quantification (LLOQ) was 1 ng/mL. Intra-day and inter-day precision RSD of isorhynchophylline in rat plasma were lower than 15%. Accuracy range was between 88.1 and 106.1 %, recovery was higher than 81.8%, and matrix effect was between 95.0 and 97.1%. The method was successfully applied in the pharmacokinetics of isorhynchophylline in rats after intravenous administration. The main pharmacokinetic parameters t(1/2), CL, and V were 2.6 +/- 1.9 h, 8.2 +/- 4.4 L/h/kg, and 27.5 +/- 18.1 L/kg, respectively.