Pharmacokinetic study of ursolic acid and its amino acid ester prodrugs in rats
Objective To develop an ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method for the determination of ursolic acid in rat plasma,and to explore the changes in pharmacokinetic of ursolic acid and its derivatives in rats.Methods Male rats were intragastrically given 70 mg·kg-1(measured by ursolic acid content)ursolic acid,ursolic acid-Vitamin E polyethylene glycol succinate(TPGS),ursolic acid phenylalanine sarcosine ester hydrochloride-TPGS.Precipitated protein was used to pretreat plasma samples.Celecoxib was used as an internal standard substance.The determination was performed on Acquity UPLC®BEH C18(50 mm×2.1 mm,1.7 μm)column with mobile phase consisted of 0.025%ammonia acetonitrile-10 mm ammonium acetate 0.1%ammonia solution(V∶V=70∶30)at a flow rate of 0.4 mL·min-1.The multiple reaction monitoring mode was performed in negative ion mode with atmospheric pressure chemical ionization source.Results The linear range of ursolic acid in plasma ranged from 100 to 10 000 μg·L-1.Compared with active pharmaceutical ingredient,the bioavailability of ursolic acid in ursolic acid-TPGS group and ursolic acid phenylalanine sarcosine ester hydrochloride-TPGS group were increased by 8.43 times and 19.52 times respectively(P<0.05).Conclusion The oral bioavailability of ursolic acid in rats is low,and the precursor drug ursolic acid phenylalanine sarcosine ester hydrochloride can improve the oral bioavailability of ursolic acid.The method is suitable for the determination of ursolic acid in rat plasma.
NETL
NSTL
万方数据
