Pharmacokinetic Of Ursolic Acid And Ursolic Acid-ethanol Cocrystal In Rats

Objective A High Performance Liquid Chromatography-Mass Spectrometric method was established to determinate concentration of ursolic acid in rats plasma.Pharmacokinetics were determinated by ursolic acid in rats.Effects of cocrystal technology and adding sodium dodecyl sulfate on the bioavailability of ursolic acid were studied in this paper.Methods The rats were given ursolic acid,ursolic acid-ethanol cocrystal,ursolic acid with sodium dodecyl sulfate and ursolic acid-ethanol cocrystal with sodium dodecyl sulfate by oral.Blood was sampled from the posterior orbital venous plexus of rats at 0,0.25,0.5,0.75,1,1.5,2,3,4,5,6,8,10 and 12 h after drug administration(blood was extra sampled of rats at 7,9 h and 24 h after drug with sodium dodecyl sulfate).Plasma was extracted with ethyl acetate and determined by HPLC-MS,then the plasma concentration of ursolicc acid–time curve was drawn.The chromatographic condition: Stationary Phase: SinoPak-C18 chromatographic column(4.6 mm×250 mm and 5.0 ?m);The mobile phase was consisted of methanol-water(90:10,0.02% triethylamine included);flow rate: 0.5 mL/min;column temperature: 25 oC;injection volume: 10 ?L;collection: SIM(Selective ion monitoring,SIM);ion polarity: negative;ionization method: electrospray ionization;detecting objects: m/z 455.7 for ursolic acid and m/z 470.6 for IS;N2 volume flow: 35.0 L/min;heating temperature: 350 oC.Calculation of the pharmacokinetic parameters was performed using the DAS 2.0 pharmacokinetic software of Chinese pharmacological society.Results The linear over the range of ursolic acid was 10~640 ng/mL,the lower limit of quantification was 10 ng/mL,intra day and inter day precision(RSD)was less than 10%,average extraction recovery rate was(80.57±5.0)%.The drug-time curve course of ursolic acid in rats was consistent with one compartment model,The drug-time curve course of ursolic acid with sodium dodecyl sulfate in rats was consistent with two compartment model.After the gavage administration of ursolic acid,ursolic acid-ethanol cocrystal,ursolic acid with sodium dodecyl sulfate and ursolic acid-ethanol cocrystal with sodium dodecyl sulfate.AUC0-12 h were(171.06±11.44),(279.68±22.94),(625.78±17.80)and(681.38±12.80)h·ng/mL,AUC0-? were(297.87±65.94),(352.88±45.04),(771.00±50.51)and(815.18±32.95)h·ng/mL,Cmax were(44.01±2.79),(83.48±4.09),(105.85±5.59)and(122.01±4.60)ng/mL.Pharmacokinetic parameters have significant differences(p<0.05)from the analysis of variance.Conclusions The method is accurate,reliable,specific and suitable for the determination of ursolic acid concentration in rats plasma,in addition to pharmacokinetics of ursolic acidethanol cocrystal in rats.The bioavailability was significantly improved after ursolic acidethanol cocrystal and adding sodium dodecyl sulfate in oral administration.