Pharmacokinetics Study Of Ponicidin In Beagle Dog

Background:Ponicidin is one of the major anti-tumor constituents of Rabdosia rubescens. Studies have shown that it has significant anti-angiogenic activity of the original. Laboratory data have also shown that ponicidin can significantly inhibit the human myeloma cell, liver cell proliferation and induce apoptosis, more effectively inhibit thegeneration and proliferation of breast cancer cells. These studies indicate that ponicidin is expected to become a natural anti-tumor drugs. But so far, the concentration of ponicidin has not been measured in the Beagle dog plasma with HPLC, and no information about the pharmacokinetic characteristics of it in Beagle dog was reported.Objective:This article aims to establish a specific, simple high-performance liquid chromatography method used to determine the concentration of ponicidin in the Beagle dog plasma, and to clarify the pharmacokinetic characteristics of ponicidin in Beagle dog after the intravenous injection. These studies provide a basis for further development and utilization on ponicidin.Method:500μL Beagle dog plasma samples containing ponicidin, added20μL phenacetin solution as the internal, was extracted by ethyl acetate. An C18column was used to separate ponicidin in plasma with methanol-0.5%triethylamine (34:66,v/v) as mobile phase, at a flow rate of1mL/min,injection volume:20μL. Uvdetector was used and the maximun absorption wavelength was set at232nm.Results:Ponicidin in the range50.0～4000ng/mL showed a good linear relationship (r2=0.9995), and the lowest limit of quantification (LLOQ) achieved was50.0ng/mL. The extraction recoveries of sample in the plasma were greater than80%, and the intra-and inter-day precision were less than10.0%, in line with biological sample analysis requirements. Plasma sample preparation was simple and did not interfere with the determination of the endogenous substances. The plasma concentration-time data obtained in dogs, fitted with3P97software to AIC as a goodness of fit index was used to determine the compartment model and calculate the pharmacokinetic parameters.Conclusion:The HPLC method was established for the first time to analyze ponicidin in Beagle dog plasma. This quantitative analysis method established was rapid, sensitive, easy to operate. The method was successfully used to study the pharmacokinectic of ponicidin in Beagle dog plasma.