论文部分内容阅读
目的:研究升麻苷H-2在大鼠体内药代动力学特征及生物利用度。方法:建立大鼠血浆中升麻苷H-2的LC-MS-MS测定方法,考察大鼠静脉注射升麻苷H-2,灌胃升麻苷H-2和升麻提取物后升麻苷H-2的血药浓度变化,并用DAS 2.0药动学数据处理软件计算药动学参数。结果:(ESI-)离子化条件下多反应监测方式进行扫描,用于定量分析的离子反应分别为m/z 635.5→131.1(升麻苷H-2)和783.5→161.1(Rg3,内标),升麻苷H-2在0.5～500μg.L-1线性良好。平均回收率>87.0%,日内、日间RSD均<11%。大鼠静脉注射升麻苷H-2单体,t1/2为1.03 h,CL为691 mL.h-1.kg-1,灌胃升麻苷H-2和升麻提取物,Tmax分别为0.5,4.0 h,绝对生物利用度分别为21.2%,36.7%。结论:该方法灵敏、快速、准确,可用于大鼠血浆中升麻苷H-2的浓度测定及临床前药代动力学研究。比较升麻提取物和升麻苷H-2单体口服给药后的药代动力学参数和生物利用度,表明升麻提取液中的其他成分对升麻苷H-2有促进其吸收的作用,或升麻苷之间存在相互代谢转化,为升麻制剂研制和临床应用提供实验依据。
Objective: To study the pharmacokinetics and bioavailability of aconite H-2 in rats. Methods: LC-MS-MS method was established to determine the content of cortisone H-2 in rat plasma. The effects of intravenous injection of cortisone H-2, Glycoside H-2 plasma concentration changes, and use the DAS 2.0 pharmacokinetic data processing software to calculate pharmacokinetic parameters. Results: (ESI-) ionization conditions were monitored by multiple reaction monitoring. The ion reactions used for quantitative analysis were m / z 635.5 → 131.1 (aconitine H-2) and 783.5 → 161.1 (Rg3, internal standard) The calibration curves were linear in 0.5-500μg.L-1. The average recovery rate was> 87.0%. The intra-day and inter-day RSDs were <11%. The rats were given intravenous injection of cortisone H-2 monomer at t1 / 2 of 1.03 h, CL of 691 mL · h-1.kg-1, 0.5,4.0 h, the absolute bioavailability were 21.2%, 36.7%. Conclusion: The method is sensitive, rapid and accurate and can be used to determine the concentration of cortisol H-2 in rat plasma and preclinical pharmacokinetics. The pharmacokinetic parameters and bioavailability after oral administration of the cohosh extract and the coenzyme H-2 monomer were compared to show that the other components in the cohosh extract had a significant effect on the absorption of the cohosh H-2 Role, or the synergy between the conversion of cortisol for cimicifuga preparation and clinical application of experimental basis.