In vivo pharmacokinetics of Xianlingpi granules based on UPLC-QQQ-MS
Objective To determine the pharmacokinetics and integrative pharmacokinetic behaviours of the main components of Xianlingpi granules in rat plasma,and the rational of the time interval for long-term clinical dosing of Xianlingpi granules.Methods Totally 12 male SD rats were divided into two groups randomly(a treatment group and a blank group),and the rats in the treatment group were given Xianlingpi granules at 8.1 g/(kg·d).After 7 days of continuous intragastric administration,0.5 mL blood was collected from the retor-orbital venous plexus of the rats before the dose and at 0.25,0.5,1,2,3,4,6,8 and 12 h after the administration.The concentration of epimedoside A,epimedin A,epimedin B,epimedin C,icariin,baohuoside Ⅱ,icariside Ⅰ,and baohuoside Ⅰ in the rat plasma at different time points were determined with UPLC-QQQ-MS,and intergrated weight coefficients were assigned for the anti-osteoporosis efficacy of 8 components respectively.DAS 3.2.8 software was used to calculate the pharmacokinetic parameters of the plasma and obtain the plasma concentration-time profiles.Results After multiple consecutive administrations in the rats,the intraplasma pharmacokinetic parameters of the 8 components showed tmax of 0.5 h,Cmax of 1.36～48.76 ng·mL-1,t1/2 of 8.50～81.40 h,anAUC0～t of 14.52～138.19 ng·mL-1·h,and MRT0～t of 3.27～5.96 h.After deducting the concentration of plasma components at the time point of 0 h,the tmax of all components in the plasma was 0.5 h,Cmax was 0.18～40.37 ng·mL-1t1/2 was 1.00～3.00 h,AUC0～t was 0.40～37.49 ng·mL-1·h and MRT0～t was 1.51～4.41 h.After assigning weight coefficients to the anti-osteoporosis efficacy of the 8 components,the pharmacokinetic parameters for component integration such as tmax was 0.5 h,and t1/2 was(1.92±0.42)h.Conclusion By studying the pharmacokinetic in plasma,the rationality of the clinical administration time interval of Xianlingpi granules is elucidated,providing reference for the material basis for the anti-osteoporosis efficacy of Xianlingpi granules.
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