补中益气汤6个成分在大鼠体内的药代动力学研究

Pharmacokinetic Study of Multiple Active Components from Buzhong Yiqi Decoction after Oral Administration in Rats by LC-MS/MS

目的考察补中益气汤中6种成分在大鼠血浆中的药动学行为。方法大鼠灌胃给予该药物稀释液(9.47 g/kg)后取血,LC-MS/MS法测定血药浓度,DAS3.1.1软件计算药动学参数。结果黄芪甲苷、毛蕊异黄酮、甘草酸、甘草次酸、柴胡皂苷D和阿魏酸的Tmax分别为(1.70±0.27)h,(0.35±0.24)h,(1.86±1.53)h,(8.40±2.19)h,(0.63±0.49)h和(0.233±0.09)h;T1/2分别为(6.21±2.28)h,(5.28±2.32)h,(4.25±1.25)h,(8.33±2.18)h,(10.11±2.40)h和(3.49±1.53)h;Cmax分别为(8.57±4.90)ng/mL,(130.16±39.00)ng/mL,(172.60±94.69)ng/mL,(956.8±523.03)ng/mL,(13.85±9.23)ng/mL,(334.00±192.10)ng/mL;AUC0-t分别为(42.81±17.30)h·ng/mL,(321.93±140.69)h·ng/mL,(508.25±136.90)h·ng/mL,(18250.17±15081.38)h·ng/mL,(18.62±11.81)h·ng/mL,(320.09±119.30)h·ng/mL。结论补中益气汤的上述6个成分中毛蕊异黄酮、柴胡皂苷D和阿魏酸的吸收较快,所建方法快速、精确、可靠,适用于补中益气汤的药代动力学研究。

Objective To investigate the pharmacokinetic characters of six active components from Buzhong Yiqi Decoction after oral administration in rats.Methods After oral administration of Buzhong Yiqi Decoction(9.47 g/kg body weight) in rats,plasma concentrations of astragaloside IV,calycosin,glycyrrhizic acid,enoxolone,ferulic acid and saikosaponin D were measured by LC-MS/MS.The PK parameters were calculated and evaluated by using DAS 3.1 software.Results Tmax of astragaloside IV,calycosin,glycyrrhizic acid,enoxolone,saikosaponin D and ferulic acid was(1.70±0.27)h,(0.35±0.24)h,(1.86±1.53)h,(8.40±2.19)h,(0.63±0.49)h and(0.233±0.09)h.T1/2 of astragaloside IV,calycosin,glycyrrhizic acid,enoxolone,saikosaponin D and ferulic acid was(6.21 ± 2.28)h,(5.28 ±2.32)h,(4.25±1.25)h,(8.33 ± 2.18)h,(10.11±2.40)h and(3.49±1.53)h.Cmax of astragaloside IV,calycosin,glycyrrhizic acid,enoxolone,saikosaponin D and ferulic acid were(8.57±4.90)ng/mL,(130.16±39.00)ng/mL,(172.60±94.69)ng/mL,(956.8 ±523.03)ng/mL,(13.85±9.23)ng/mL and(334.00±192.10)ng/mL.AUC0-t of astragaloside IV,calycosin,glycyrrhizic acid,enoxolone,saikosaponin D and ferulic acid were(42.81±17.30)h·ng/mL,(321.93±140.69)h·ng/mL,(508.25±136.90)h·ng/mL,(18250.17±15081.38)h·ng/mL,(18.62±11.81)h·ng/mL and(320.09±119.30)h·ng/mL.Conclusion Calycosin,saikosaponin D and ferulic acid were rapidly absorbed in plasma after oral administration of Buzhong Yiqi Decoction.A rapid,sensitive and specific HPLC-MS/MS method was developed and validated for simultaneous determination of astragaloside IV,calycosin,glycyrrhizic acid,enoxolone,saikosaponin D and ferulic acid in plasma samples.