布渣叶总黄酮中牡荆苷、异牡荆苷、水仙苷在家兔体内的药动学

Pharmacokinetics of vitexin,isovitexin and narcissus glycosides from total flavonoids of Microcos paniculata L.in rabbits

目的:建立了家兔灌胃布渣叶总黄酮提取物后血浆中牡荆苷、异牡荆苷、水仙苷的HPLC/MS方法,并研究其药动学。方法:家兔灌胃给于布渣叶总黄酮提取物后于不同时间点取血,采用HPLC/MS测定兔血浆中牡荆苷、异牡荆苷、水仙苷的血药浓度,并计算药动学参数。色谱柱:Hypersil Gold C_(18)柱(250 mm×4.6 mm,5μm),流动相为乙腈-1%乙酸水溶液(V/V),梯度洗脱,柱温20℃,质谱检测采用ESI离子源,同时测定血浆样品中牡荆苷、异牡荆苷、水仙苷的浓度,采用非房室模型估算药动学参数。结果:牡荆苷、异牡荆苷、水仙苷均在0.2~20 mg·L^(-1)内线性关系良好(r>0.999),提取回收率、精密度和稳定性均良好。家兔口服布渣叶总黄酮提取物后牡荆苷、异牡荆苷、水仙苷的主要药动学参数如下:AUC0-t分别是10.13,8.92,15.12 mg·L^(-1)·h,Cmax分别是3.04,2.62,3.51 mg·L^(-1),tmax分别是0.75,0.75,1.00h,t1/2分别是2.96,3.20,3.93 h,MRT0-∞分别是5.01,5.58,6.33 h。结论:该方法可特异、准确、灵敏地同时测定家兔血浆中牡荆苷、异牡荆苷、水仙苷的血药浓度,家兔口服布渣叶总黄酮提取物后牡荆苷、异牡荆苷、水仙苷可迅速吸收入体内,其药时曲线存在双峰现象。

OBJECTIVE To develop a HPLC/MS method for measurement of vitexin,isovitexin and narcissus glycosides in rabbit plasma after intragastric infusion of total flavonoids of Microcos paniculata L.,and to study pharmacokinetics of vitexin,isovitexin and narcissus glycosides in rabbits.METHODS Plasma samples were collected at different time points after rabbits were orally administered total flavonoids of Microcos paniculata L.Plasma concentrations of vitexin,isovitexin and narcissus glycosides were analyzed by HPLC-MS method.Analytes were separated on a Hypersil Gold C18 column（250 mm×4.6mm,5μm）,and mobile phase consisting of acetonitrile and 1% acetic acid aqueous solution was programmed in a linear gradient mode.Column temperature was 20℃.Compounds were ionized in electro-spray ionization ion source of mass spectrometer.Pharmacokinetic parameters were assessed with non-compartment model.RESULTS Relationships between concentrations and peak areas of three compounds were linear（r〉0.999）.Precisions,accuracy and stability of analytes all met the requirements.Main pharmacokinetic parameters of vitexin,isovitexin and narcissus glycosides after oral administration were as follows：AUC0-t,Cmax,tmax,t1/2and MRT0-∞were 10.13 mg·L-1·h,3.04 mg·L-1,0.75 h,2.96 h and 5.01 h for vitexin,8.92 mg·L-1·h,2.62 mg·L-1,0.75 h,3.02 h and 5.58 h for isovitexin,and 15.12 mg·L-1·h,3.51 mg·L-1,1.00 h,3.93 h and6.33 h for narcissus glycosides.CONCLUSION The developed method is simple,rapid,sensitive enough and has been successfully applied to pharmacokinetic study.Plasma concentration-time curves of vitexin,isovitexin and narcissus glycosides show double peaks after intragastric administration of total flavonoids of Microcos paniculata L.