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目的:建立测定家兔血浆中栀子苷浓度的高效液相方法,研究醒脑静滴鼻液鼻腔给药后栀子苷在家兔体内的药动学过程。方法:醒脑静滴鼻液家兔鼻腔给药,给药量为12 mg.kg-1(以栀子提取物计),于给药后1,3,5,10,20,30,45,60,90,120,240 min左颈动脉采血,乙腈沉淀法处理血浆样品,HPLC测定血浆中栀子苷浓度,以Kinetica软件拟合药动学参数。结果:血浆中栀子苷在0.136 5～2.73 mg.L-1线性良好,相关系数为0.999 6,低、中、高浓度回收率分别为(97.14±3.78)%,(95.06±2.95)%,(91.50±1.82)%,其日内、日间精密度RSD均小于4%,符合要求。醒脑静滴鼻液鼻腔给药后,栀子苷家兔血浆药动学过程符合二室开放模型,主要药动学参数(拟合值)为Cmax为(2.013±0.563)mg.L-1,Tmax为(6.405±1.764)min,Ke为(0.032 5±0.013 3)min-1,CL为(0.059 3±0.024 6)L.min-1.kg-1,AUC为(116.89±50.19)mg.min-1.L-1,MRT为(84.447±19.420)min。结论:本实验中建立的血浆处理及HPLC方法适用于家兔体内栀子苷的含量测定和药代动力学研究,醒脑静鼻腔给药后栀子苷吸收迅速,具有较好的应用前景。
Objective: To establish a HPLC method for determination of geniposide in rabbits plasma and to study the pharmacokinetics of geniposide in rabbits after nasal administration of Xingnao Jing nasal drops. Method: Nasosinus nasalis nasal solution was given to nasal cavity of rabbits for 12 mg.kg-1 (taking gardenia extract) as the control group. The rats were given 1,3,5,10,20,30,45 60, 90, 120 and 240 min. The blood samples were taken from the left carotid artery and the plasma was collected by acetonitrile precipitation method. The concentration of geniposide in plasma was determined by HPLC. The pharmacokinetic parameters were fitted by Kinetica software. Results: The linearity of geniposide in plasma was 0.136 5 ~ 2.73 mg.L-1, the correlation coefficient was 0.999 6, and the recoveries of geniposide in plasma were (97.14 ± 3.78)% and (95.06 ± 2.95)%, respectively (91.50 ± 1.82)%, the intra-day and inter-day precision RSD were less than 4%, in line with the requirements. The pharmacokinetics of geniposide in rabbits accorded with the two-compartment open model after nasal administration of Xingnaojing intravenous nasal drops. The main pharmacokinetic parameters (fitted values) were Cmax (2.013 ± 0.563) mg.L-1 , Tmax was (6.405 ± 1.764) min, Ke was (0.032 5 ± 0.013 3) min-1, CL was (0.059 3 ± 0.024 6) L.min-1.kg-1 and AUC was (116.89 ± 50.19) mg .min-1.L-1, MRT was (84.447 ± 19.420) min. Conclusion: The plasma treatment and HPLC method established in this study are suitable for the determination of geniposide in rabbits and pharmacokinetic study. After intravenous administration of Xingnaojing intranasal administration, geniposide is absorbed rapidly and has good application prospect.