三七提取物大鼠体内3种皂苷成分测定方法建立及药代动力学研究

Establishment of a method for determination of three saponins composition from Panax notoginseng extract in rats and pharmacokinetic study

对建立HPLC-MS/MS测定SD大鼠血浆中三七皂苷R1、人参皂苷Rg1、Rb1浓度的方法进行方法学验证,并研究三七提取物在SD大鼠体内的药代动力学.SD大鼠灌胃给予三七提取物1500 mg/kg后采集血样,HPLC-MS/MS测定血浆中Rg1、Rb1和R1的质量浓度,并利用DAS软件计算药动学参数.建立的HPLCMS/MS方法特异性良好,连续3批标准曲线相关系数均大于0.99(权重1/X2);血浆中3种成分的低、中、高3个质量浓度的日内精密度(RSD)均小于10%,准确度为88%~105%,日间精密度(RSD)均小于15%,准确度为93%~109%;冻融及室温稳定性良好,基质效应不影响测定.采用非房室模型计算Rg1、Rb1和R1在大鼠体内的药代参数,结果表明,平均AUC0−t、ρmax、t1/2、MRT0−t的数值大小为Rb1>>Rg1>R1;平均Tmax的数值大小为Rb1>>R1>Rg1.所建立的HPLC-MS/MS方法适用于三七提取物中Rg1、Rb1、R1在大鼠体内的药代动力学研究.Rg1、R1在大鼠体内具有相似的药代特征,吸收快、消除快;Rb1在大鼠体内的药代特征与Rg1、R1差别较大,吸收慢、消除慢;Rb1在大鼠体内的血浆暴露占绝对优势.

To verify the method of HPLC-MS/MS determination of notoginsenoside R1,Ginsenoside Rg1,Ginsenoside Rb1 in plasma of SD rats,the pharmacokinetics of Panax notoginseng extract in SD rats was studied.SD rats intragastrically administered Panax notoginseng extract of 1500 mg/kg had their blood collected for the determination of plasma concentration by HPLC-MS/MS,after which pharmacokinetic parameters were calculated by DAS software.The established HPLC-MS/MS method has good specificity,and the correlation coefficients of the three consecutive batches of standard curves are all greater than 0.99(weighted 1/X2).The linearity of each component in certain concentration ranges was good.The RSD day precision of three components in plasma were less than 10%and the accuracy ranged from 88%to 105%.The diurnal precision(RSD)was less than 15%and the accuracy was between 93%to 109%.The stability of freeze-thaw and room temperature was good.The matrix effect does not affect the measurement effect.The non-compartmental model was used to calculate the pharmacokinetic parameters of Rg1,Rb1 and R1 in rats.The results showed that the average values of AUC0-t,ρmax,t1/2,and MRT0-t,Rb1>>Rg1>R1;average Tmax value of Rb1>>R1>Rg1.The established HPLC-MS/MS method is suitable for the pharmacokinetic study of Rg1,Rb1 and R1 in Panax notoginseng extract in rats.Rg1 and R1 have similar pharmacokinetic characteristics in rats,with rapid absorption and fast elimination;Rb1 pharmacokinetic characteristics in rats are very different from Rg1 and R1,with slow absorption and slow elimination;Rb1 exposure inplasma of rats take the absolute advantage.