银荷降脂方中5种活性成分在大鼠体内的药代动力学研究

目的: 建立液相色谱质谱联用定量分析方法,测定大鼠血浆中荷叶碱、去甲氧基姜黄素、金丝桃苷、芹菜素及槲皮素的含量,并用于银荷降脂方中主要活性成分经口服给药后大鼠体内药代动力学研究。方法: 采集SD大鼠灌胃银荷降脂方后不同时间点的血浆样本,采用LC-MS/MS以多反应离子监测(MRM)模式,电喷雾离子源(ESI)正、负离子检测,测定血浆中荷叶碱、去甲氧基姜黄素、金丝桃苷、芹菜素及槲皮素5种成分的浓度,应用DAS3.2软件进行药动学参数计算。结果: 荷叶碱、去甲氧基姜黄素、金丝桃苷、芹菜素、槲皮素T_max分别为(1.10±0.22)、(0.19±0.04)、(0.20±0.05)、(0.17±0.00)、(0.17±0.00)h,C_max分别为(52.10±7.42)、(1.61±0.50)、(106.02±49.59)、(28.07±9.76)、(186.79±60.99)ng · mL^-1,t_1/2分别为(2.82±0.69)、(6.46±0.63)、(16.04±9.65)、(5.16±2.12)、(8.27±7.04)h,AUC_0-t分别为(167.33±42.61)、(5.86±4.42)、(261.73±34.72)、(78.99±18.20)、(683.04±173.96)ng · h · mL^-1,MRT_0-t分别为(4.59±0.51)、(7.87±1.66)、(8.43±1.22)、(8.32±1.23)、(7.43±1.26)h。结论: 本文建立的LC-MS/MS法符合方法验证要求,可用于银荷降脂方中荷叶碱、去甲氧基姜黄素、金丝桃苷、芹菜素、槲皮素在大鼠体内的药动学研究,为临床应用及新药开发提供依据。

Objective: To establish an LC-MS/MS method for determination of nuciferine, demethoxycurcumin, hyperoside, apigenin, quercitin in rat plasma and apply this method to subsequently determine the pharmacokinetics of the main active ingredients in Yinhe Jiangzhi decoction. Methods: Electrospray ionization(ESI)source was applied and operated in the positive and the negative multiple reaction monitoring(MRM)mode.The blood samples were collected at different time points after Yinhe Jiangzhi decoction was orally administrated.The plasma concentration of five active ingredients was then detected by LC-MS/MS.The pharmacokinetic parameters were calculated by the DAS 3.2 software. Results: The main pharmacokinetic parameters of nuciferine, demethoxycurcumin, hyperoside, apigenin, quercitin were as follows:T_max (1.10±0.22), (0.19±0.04), (0.20±0.05), (0.17±0.00), (0.17±0.00)h;C_max (52.10±7.42), (1.61±0.50), (106.02±49.59), (28.07±9.76), (186.79±60.99)ng · mL^-1;t_1/2 (2.82±0.69), (6.46±0.63), (16.04±9.65), (5.16±2.12), (8.27±7.04)h;AUC_0-t(167.33±42.61), (5.86±4.42), (261.73±34.72), (78.99±18.20), (683.04±173.96)ng · h · mL^-1;MRT_0-t(4.59±0.51), (7.87±1.66), (8.43±1.22), (8.32±1.23), (7.43±1.26)h. Conclusion: The LC-MS/MS method established in this paper conforms to the requirements of the methodology validation, and can be applied to the pharmacokinetic research of nuciferine, demethoxycurcumin, hyperoside, apigenin and quercitin in rat plasma.These pharmacokinetic results provide useful information for clinical use and further development of novel drugs.