LC-MS法研究黄芪对附子6种乌头生物碱大鼠药代动力学的影响

Determining the effect of Huangqi on the pharmacokinetics of six different alkaloids from Fuzi in rats by LC-MS

研究黄芪-附子配伍对附子3种单酯型生物碱(苯甲酰次乌头原碱BHA、苯甲酰新乌头原碱BMA、苯甲酰乌头原碱BAC)和3种双酯型生物碱(次乌头碱HA、新乌头碱MA、乌头碱AC)的大鼠药代动力学的影响。采用LC-MS测定大鼠单次给药后不同时间血浆中药物浓度,DAS 3.3求算药物的药代动力学参数,SPSS 13.0软件分析附子配伍黄芪前后主要药动学参数差异。配伍黄芪后,6种生物碱的AUC0-t和AUC0-∞均显著降低,除HA外的5种生物碱的CLz/F升高;3种单酯型生物碱Cmax降低,tmax延长;BMA和MA的分布容积(Vz/F)增大。黄芪可以抑制附子生物碱的吸收,诱导附子生物碱向全身分布,并加快附子生物碱在体内的消除。本研究中动物实验方案已获得江西中医药大学实验动物伦理委员会的批准。

This study aimed to investigate the influence of combinating Huangqi with Fuzi on the pharmacokinetics of six Aconitum alkaloids,i.e.aconitine(AC),hypaconitine(HA),mesaconitine(MA),benzoylaconine(BAC),benzoylhypaconine(BHA)and benzoylmesaconine(BMA).The plasma concentrations of the drugs were determined by LC-MS for dose response and time dependent curves.The pharmacokinetic parameters were calculated by DAS 3.3,and SPSS 12.0 was used to analyze the differences of main pharmacokinetic parameters between the two groups.Comparing with Fuzi group,the AUC0-t and AUC0-∞of six alkaloids in Fuzi-Huangqi group was significantly decreased,the CLz/F of six alkaloids except HA was significantly increased;the Cmax was decreased and the tmax was prolonged in 3 monoester alkaloids,and the apparent volume of distribution of BMA and MA(Vz/F)increases.These data indicated that Huangqi can inhibit the absorption of aconite alkaloids,induce the distribution of aconite alkaloids to the whole body,and accelerate the elimination of aconite alkaloids.The animal experiment scheme in this study has been approved by the Experimental Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine.