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中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (2): 144-148.

• 基础研究 • 上一篇    下一篇

HPLC 法测定马兜铃酸Ⅰ在大鼠体内的浓度及其毒代动力学

徐晓月1,2, 江振洲2,3, 黄鑫2, 张陆勇2   

  1. 1河南省食品药品检验所药理室, 郑州 450003, 河南;
    2江苏省新药筛选中心,南京 210038, 江苏;
    3中国药科大学药物质量与安全预警教育部重点实验室, 南京 210038, 江苏
  • 收稿日期:2007-06-05 修回日期:2008-01-18 出版日期:2008-02-26 发布日期:2020-10-14
  • 通讯作者: 张陆勇, 男, 研究员, 博士生导师, 研究方向:药理毒理和药代动力学。Tel:025-83241500 E-mail:lyonzhang@cpu.edu.cn
  • 作者简介:徐晓月, 女, 博士, 研究方向:药理毒理和药代动力学。Tel:0371-63388238  E-mail:xiaoyuexu@hotmail.com
  • 基金资助:
    有毒中药质量控制及有毒成分限量示范研究课题资助项目(国中医药科2004ZX05)

Determination of aristolochic acid Ⅰ in rats by HPLC and its toxicokinetics

XU Xiao-yue1,2, JIANG Zhen-zhou2,3, HUANG Xin2, ZHANG Lu-yong2   

  1. 1Department of Pharmacology, Henan Provincial Institute of Food and Drug Control, Zhengzhou 450003, Henan,China;
    2Jiangsu Center for Drug Screening, Nanjing 210038, Jiangsu, China;
    3Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210038, Jiangsu,China
  • Received:2007-06-05 Revised:2008-01-18 Online:2008-02-26 Published:2020-10-14

摘要: 目的:建立大鼠血浆中马兜铃酸Ⅰ的HPLC测定方法, 采用单次灌胃给药毒性研究的3种剂量对马兜铃酸Ⅰ进行毒代动力学的初步研究, 了解在毒性实验条件下马兜铃酸Ⅰ所达到的全身暴露与毒性之间的内在联系。方法:大鼠分别灌胃给予马兜铃酸Ⅰ 100、30、10 mg/kg, 测定不同时间点的血浆药物浓度, 应用统计矩的方法对血药浓度-时间数据进行拟合并计算毒代动力学参数。结果:测定方法的最低定量浓度为0.02 mg/L, 线性范围为0.02 ~ 40.00 mg/L, 回收率在82.4 %~101.2 %之间, 日内、日间RSD 小于1.0 %。100、30、10 mg/kg 3 个剂量组的主要毒代动力学参数如下:t1/2α分别为(0.8 ±0.4)、(0.9 ±0.7)、(1.0 ±0.8) h ;t1/2β分别为(34 ±19)、(133 ±64)、(114 ±50) h ;tmax 分别为(0.31 ±0.12)、(0.25 ±0.00)、(0.38 ±0.19) h ;Cmax 分别为(3.0 ±1.7)、(1.1 ±0.7)、(1.0 ±0.7) mg/L ;AUC(0-48) 分别为(18 ±3) 、(18 ±2) 、(21 ±5) mgL-1 。h。结论:该方法重现性好、灵敏度高, 适用于大鼠血浆中马兜铃酸Ⅰ的测定。马兜铃酸Ⅰ能迅速吸收入血, 随后快速分布、缓慢消除。在毒性剂量下, 马兜铃酸Ⅰ在大鼠体内的毒代动力学过程具有非线性动力学性质。

关键词: HPLC, 马兜铃酸Ⅰ, 单次灌胃给药, 毒代动力学, 统计矩

Abstract: AIM:To establish an HPLC method for the determination of aristolochic acid Ⅰ in rat plasma, study the toxicokinetics of aristolochic acid Ⅰ at the three doses adopted in toxicology research and realize the relationship between the exposure level and toxicity.METHODS:Plasma concentrations at different time were determined after single oral administration at the dose of 100, 30 and 10 mg/kg.The data of concentration-time were fitted and the toxicokinetics parameters were calculated by statistical moment then. RESULTS:The limit of quantitation was 0.02 mg/L, the linear range was 0.02 ~ 40.00 mg/L.The average recovery was between 82.4 % ~ 101.2 %.The intraday and inter-day RSD were less than 1.0 %.The parameters of high, middle and low doses were as follows:t1/2α were (0.8 ±0.4), (0.9 ±0.7) and (1.0 ±0.8) h, t 1/2β were (34 ±19), (133 ±64) and (114 ±50) h, tmax were (0.31 ±0.12), (0.25 ±0.00) and (0.38 ±0.19) h, Cmax were (3.0 ±1.7), (1.0 ±0.7) and (1.0 ±0.7) mg/L, AUC(0-48) were (18 ±3), (18 ±2) and(21 ±5) mgL -1。h, respectively.CONCLUSION:The method was sensitive, specific and suitable for the analysis of concentrations of aristolochic acid Ⅰ in rat plasma.The absorption of aristolochic acid Ⅰ was quick after single oral administration, and then it was distributed fast and eliminated slowly in the plasma.It was indicated the nonlinear toxicokinetics characteristic of aristolochic acid Ⅰ took place in the studied dose range.

Key words: HPLC, aristolochic acid Ⅰ, single oral administration, toxicokinetics, statistical moment

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