Determination of 8-methoxypsoralen in mouse plasma by high performance liquid chromatography and its application to pharmacokinetic study / 北京大学学报(医学版)

OBJECTIVE@#To establish a high performance liquid chromatography (HPLC) method for the determination of 8-methoxypsoralen (8-MOP) in mouse plasma and apply it to a pharmacokinetic study of 8-MOP.@*METHODS@#8-MOP was separated on a Waters Symmetry18 column (250 mm × 4.6 mm, 5 μm) and determined by HPLC using isocratic elution, and 5-methoxypsoralen was used as internal standard. The mobile phase consisted of methanol-water (55:45, V/V) at a flow rate of 1.0 mL/min. The excitation and emission wavelength of fluorescence detector were set at 334 nm and 484 nm respectively, and the internal standard method was used for quantitative analysis. In the study, 60 healthy ICR male mice were randomly divided into twelve groups. The mice in control group were administered intragastrically with 1% Tween 80, and the mice in the other eleven groups were administered intragastrically with 8-MOP (40 mg/kg). Plasma concentrations of 8-MOP in the mice at different time points after treatment were determined by HPLC. Pharmacokinetic parameters were calculated by DAS 2.0 software.@*RESULTS@#The calibration curve of 8-MOP was linear with a correlation coefficient of 0.999 3 over the concentration range of 0.05 to 10 mg/L, and the limit of detection was 0.015 mg/L. The average recoveries of 8? MOP at three different concentrations (0.10, 0.50, 2.5 mg/L) were from 92.5% to 100.6%. The intra-day precision of 8-MOP was from 3.3% to 8.2%, while the inter-day precision was from 3.4% to 6.7% at three spiked concentration levels. The extraction recoveries of 8-MOP were from 90.9% to 92.0%, and the plasma samples could be stored at -80°C for 15 days at least at three spiked concentration levels. 8-MOP could be detected in mouse plasma 5 min after intragastrical administration to the mice (1.4 mg/L). The concentration of 8-MOP in the mouse plasma reached a maximum 2 h after administration, and 8-MOP could still be detected 24 h after administration (1.1 mg/L). t1/2 was (39.21±3.65) h, Cmax was (2.31±0.02) mg/L, tmax was (2.00±0.00) h, and AUC0-t was (33.34±1.19) (h×mg)/L.@*CONCLUSION@#The proposed method is accurate and simple,suitable for pharmacokinetics of 8-MOP in mice.

Effect of roots of Ficus hirta on cocaine-induced hepatotoxicity and active components / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of the roots of F. hirta against the cocaine-induced hepatotoxicity and it's active components.</p><p><b>METHOD</b>Cocaine hydrochloride was subcutaneously injected to make male ICR mice liver wounded. Male ICR mice were randomly ig administered with the F. hirta decoction. The dose groups are 100, 200, 300 g x kg(-1) herb materials per body weight. Cocaine hydrochloride was subcutaneously injected into the mice after the administration. The serum ALT, AST activity and the activity of CAT in liver homogenate were assayed, and liver change of pathomorphism was evaluated to prove the effect of the F. hirta decoction on cocaine-induced hepatotoxicity. And the activity of psoralean which was separated from the F. hirta decoction by bioassay-guided fractionation, was proofed in the same method.</p><p><b>RESULT</b>We find that the F. hirta decoction shows a distinct effect on reducing serum transferase. The serum transferase and the content CAT in liver homogenate were dose-related reduced, and the histopathological examination found a significantly change of the liver tissues. And the psoralean, qua the mainly component, shows the same effect.</p><p><b>CONCLUSION</b>F. hirta has the protective effect against the cocaine-induced hepatotoxicity. Psoralean is the basis.</p>