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| HPLC法测定马兜铃酸Ⅰ在大鼠体内的浓度及其毒代动力学 | |
| 引用本文： | 徐晓月,江振洲,黄鑫,张陆勇.HPLC法测定马兜铃酸Ⅰ在大鼠体内的浓度及其毒代动力学[J].中国临床药理学与治疗学,2008,13(2):144-148. |
| 作者姓名： | 徐晓月 江振洲 黄鑫 张陆勇 |
| 作者单位： | 1. 河南省食品药品检验所药理室,郑州,450003,河南;江苏省新药筛选中心,南京,210038,江苏 2. 江苏省新药筛选中心,南京,210038,江苏;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 3. 江苏省新药筛选中心,南京,210038,江苏 |
| 基金项目： | 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 |
| 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Ⅰ100、30、10mg／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0．02mg／L，线性范围为0．02～40．00mg／L，回收率在82．4％～101．2％之间，日内、日间RSD小于1．0％。100、30、10mg／kg3个剂量组的主要毒代动力学参数如下：t1/2a分别为（0．8±0．4）、（0．9±0．7）、（1．0±0．8）h；t]1／2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）mg·L^-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 |
| 文章编号： | 1009-2501(2008)02-0144-005 |
| 修稿时间： | 2007年6月5日 |
Determination of aristolochic acid Ⅰ in rats by HPLC and its toxicokinetics |
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| XU Xiao-yue,JIANG Zhen-zhou,HUANG Xin,ZHANG Lu-yong.Determination of aristolochic acid Ⅰ in rats by HPLC and its toxicokinetics[J].Chinese Journal of Clinical Pharmacology and Therapeutics,2008,13(2):144-148. | |
| Authors: | XU Xiao-yue JIANG Zhen-zhou HUANG Xin ZHANG Lu-yong |
| Institution: | XU Xiao-yue, JIANG Zhen-zhou, HUANG Xin, ZHANG Lu-yong(Department of Pharmacology, Henan Provincial Institute of Food and Drug Control, Zhengzhou 450003, Henan, China ; 2Jiangsu Center for Drug Screening, Nanfing 210038, Jiangsu , China ; 3Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210038, Jiangsu, China) |
| Abstract: | AIM： To establish an HPLC method for the determination of aristoloehic acid Ⅰ in rat plas-ma, 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 concentrationotime 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： t1/2a were （0.8±0.4）, （0.9±0.7） and （1.0±0.8） h, t1/2β 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） mg·L^-1·h, respectively. CONCLUSION： The method was sensitive, specific and suitable for the analysis of concentrations of aristolochic acid Ⅰ in mt 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. |
| Keywords: | HPLC aristolochic acid Ⅰ single oral administration toxicokinetics statistical moment |
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