THE DETERMINATION OF CONCENTRATION OF HARMALINE IN THE PLASMA OF RABBITS AND MICE BY HPLC AND STUDY ON THE PHARMACOKINETICS QF HARMALINE
XU Zhao-Dong PAN Qi-Chao (Cancer Institute, Sun Yat-sen University of Medical Sciences, Guangzhou 510060 )
The concentrations of harmaline in the plasma of New Zealand white rabbits and mice were determined by HPLC and the pharmacokinetic of this drug was studied.The HPLC system of Waters Corporation (Japan) and C18 ion exchange resin column was used. The mobile phase is acetonitrile: water=70: 30(v/v), containing citric acid 0.05M, pH 4.0, flow rate is 0.8mi/min, detection wavelength 370 nm. The minimal detectable concentration is 0.02 μg/ml. The retention time of harmaline is 7.75-8.0min and that of the internal standard(m-AMSA) is 6.25-6.50 min.In 4 among 6 white New Zealand rabbits the pharmacokinetics conformed one compartment open model and in two rabbits two compartment model. In five rabbits after iv injection of 10 mg/kg, the T1/2 was found to be 138.8 ±60.4 min.The concentration of harmaline in plasma of mice after ip injection of effective antitumor dose were determined by HPLC. The peak levels were achieved 10 min after injection. The maximal concentrations were found to be 3.09, 5.80, 7.75 μg/ml The concentration of harmaline in plasma could be detected 8 hours after injection. The T1/2were 316.6 min (after 22.5 mg/kg ip×1), 263.76 min(after 45mg/kg ip×1) and 212.93 min(after 45mg/kg/d ip×8)in mice.