摘要
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 investigate the pharmacokinetic properties of cimicifugoside H-2 in rats, and the absolute bioavailability of cimicifugoside H-2 in vivo were also scarcely reported. Method： SD rats were administrated an intravenous dose of cimicifugoside H-2 （5 mg .kg-1） and oral dose of cimicifugoside H-2 （5 mg kg-1 ） or Cimicifuga foetida extract （50 mg＇kg）, respectively. At different time points, the concentrations of cimicifugoside H-2 in rat plasma were determined by LC-MS-MS method. Main pharmacokinetics parameters were estimated by non-compartmental analysis using the DAS 2.0 software. Result： The curves showed excellent linear regressions within the range of tested concentrations. The intra-and inter-day variations were below 11% in terms of RSD. The recoveries were 87.0%-91.6% for spiked cimicifugoside H-2 samples. The PK parameters after iv administration of individual cimicifugoside were respectively：elimination half-life 1.03 h-1; clearance 691 mL ·h-1. kg-l. PK parameters following oral administration of the extract and cimicifugoside H-2 was respectively： Tmax 0.5 and 4.0 h. Absolute oral bioavailability （F） was 21.2% and 36.7%. Conclusion： This method proved to be specific, accurate and sensitive to be applied to the pharmacokinetics studies of H-2 in rats. Comparison of the pharmacokinetics of cimicifugoside H-2 given alone and together in rat suggest that administration of herbal preparations of Cimicifuga for clinical use may provide longer duration of action than administration of single isomers.
出处
《中国实验方剂学杂志》
CAS
北大核心
2012年第20期149-153,共5页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家"十一五"重大科技专项基金课题(2009ZX09304-003)
关键词
升麻苷H-2
药代动力学
液相色谱-串联质谱法
固相萃取
eimicifugoside H-2
pharmacokinetics
liquid chromatography-tandem mass spectrometry
solid phase extraction （SPE）
作者简介
盖芸芸，博士研究生，从事药代动力学研究，E-mail：gaiyunyun@luye．cn
[通讯作者]孙严彤，博士，讲师从事药物分析研究，Tel：0431-85619704，E-mail：sunyt@jiu．edu．cn
