天然产物研究与开发 ›› 2018, Vol. 30 ›› Issue (10): 1805-1810.doi: 10.16333/j.1001-6880.2018.10.025

• 开发研究 • 上一篇    下一篇

剂量水平与给药时程对豆腐果苷大鼠体内药代动力学的影响

贾元威,沈杰*,谢海棠,曹梦欣,项婷   

  1. 安徽省药物临床评价中心 皖南医学院弋矶山医院,芜湖 241001
  • 出版日期:2018-10-31 发布日期:2018-11-01
  • 基金资助:

    国家自然科学基金(81641141,81503236);安徽省自然科学基金(160808QH212,1408085MH163);安徽省高校自然科研重点项目(KJ2015A155);弋矶山医院引进人才基金(YR201407,YR201501);皖南医学院重点科研项目培育基金(WK2015ZF01);安徽省高校优秀青年人才支持计划(gxyqZD2016178,gxyqZD2016179);皖南医学院教学质量与教学改革工程(2016jyxm22,2017kc bz03)

     

Influence of Dosage Devels and Multiple-doses on Pharmacokinetics Behaviors of Helicid in Rats

JIA Yuan-wei, SHEN Jie*, XIE Hai-tang, CAO Meng-xin, XIANG Ting   

  1. Anhui provincial Center for Drug Clinical Evaluation,Yijishan Hospital of Wannan Medical College,Wuhu 241001, China
  • Online:2018-10-31 Published:2018-11-01

摘要: 本研究建立并验证了一种简单、快速、灵敏、可靠的超快速液相-电喷雾离子化-串联质谱方法(UFLC-ESI-MS/MS)用于定量大鼠血浆中的糖苷类化合物豆腐果苷含量。所建立的检测方法最低定量限(LLOQ)为0.1 ng/mL并在2 min之内完成。本检侧方法验证内容包括选择性、线性、准确度和精密度、回收率、离子抑制率、后遗效应、交叉干扰、残留、稀释可靠性、稳定性和已测样品再分析。应用本方法,第一次评价了豆腐果苷的生物利用度、不同剂量水平及多剂量给药对其在体内处置的影响。结果表明,胃肠道给药方式下(25、50、100 mg/kg),豆腐果苷显示出线性行为。生物利用度在三个剂量水平下分别为48.34%、48.17%和60.34%。同时,除Tmax外,多次给药(50 mg/kg,tid)不会对PK行为造成很大影响且不会引起蓄积。

关键词: 豆腐果苷, UFLC-ESI-MS/MS, 生物利用度, 药物代谢动力学

Abstract: A simple,rapid,sensitive and reliable ultra-fast liquid chromatography-electrospray ionization-tandem mass spectrometry(UFLC-ESI-MS/MS)method was developed for quantifying helicid in rat plasma.The lower limit of quantitation(LLOQ)was 0.1 ng/mL and total run time was within 2 min.The method was validated in terms of selectivity,linearity,accuracy and precision,extraction recoveries,matrix effects,carry-over,cross talk,dilution integrity,stability and incurred sample reanalysis(ISR).Using this validated method,bioavailability,influence of different dosage levels and multiple-doses on pharmacokinetic behaviors of helicid were investigated for the first time.Results showed that after intragastric(i.g.)administration at three dose levels(25,50,100 mg/kg),helicid exhibited a linear pharmacokinetic behavior.Bioavailability at three dose levels was 48.34%,48.17% and 60.34%,respectively.Meanwhile,besides Tmax,multiple-dosing of helicid(50 mg/kg,tid)for 6 days seemed not significantly affect the PK profiles and accumulation didn’t occur.

Key words: helicid, UFLC-ESI-MS/MS, bioavailability, Pharmacokinetics  

中图分类号: 

R969.1