Pharmacokinetics and tissue distribution of tetrahydropalmatine,nobiletin,and costunolide in rats after oral administration of Dalitong extract
AIM:To investigate the pharmacoki-netic properties of the main active components of Dalitong extract in SD rats after oral administration using UPLC-MS/MS.METHODS:An UPLC-MS/MS method was established to simultaneously detect tetrahydropalmatine,nobiletin and costunolide in the plasma and tissues of SD rats.The method was applied to investigate the pharmacokinetic charac-teristics and tissue distribution.RESULTS:After a single oral administration,the three active compo-nents were rapidly absorbed into the body,with a peak concentration(Cmax)of(13.73±7.50),(27.01± 17.69)and(6.73±29.94)ng/mL for tetrahydropal-matine,nobiletin,and costunolide,respectively.The time to reach the peak concentration(Tmax)was(1.40±0.93),(0.63±0.28)and(2.38±8.81)h,re-spectively.The area under the curve(AUC)was(80.43±40.03),(41.30±28.69)and(303.90±136.69)ng·h·mL-1,respectively,and the elimination half-life(t1/2)was(5.82±2.22),(1.08±0.01)and(4.95± 2.53)h,respectively.Multiple dosing significantly in-creased the exposure of the three components.There were significant differences in exposure be-tween male and female rats,with higher exposure observed in female rats(P＜0.05).The three active components were widely distributed in various tis-sues/organs,with the highest exposure observed in the gastrointestinal tract,followed by the liver and kidney.CONCLUSION:The UPLC-MS/MS method is accurate,sensitive,and reliable for the quantitative analysis of tetrahydropalmatine,nobiletin,and cos-tunolide.These three active components in Dali-tong extract can be absorbed,widely distributed in various tissues or organs,and rapidly metabolized/eliminated after oral administration.They are po-tential pharmacokinetic markers of Dalitong extract.
Dalitong extracttetrahydropalma-tinenobiletincostunolidepharmacokineticstis-sue distribution
国家科技期刊平台
NSTL
万方数据
维普
