http://jcps.bjmu.edu.cn

• 研究论文 • 上一篇    下一篇

高效液相色谱法测定大鼠血浆中灵芝酸单体T及其药动学考察

陈香, 陶少林, 高峰*, 李英波, 钟建江   

  1. 1. 华东理工大学 药学院, 上海 200237
    2. 上海交通大学 生命科学技术学院 微生物代谢教育部重点实验室, 上海 200240
  • 收稿日期:2009-12-28 修回日期:2010-03-15 出版日期:2010-05-15 发布日期:2010-05-15
  • 通讯作者: 高峰*

Quantitative determination of ganoderic acid T in rat plasma by a sensitive
RP-HPLC method and its application in pharmacokinetic studies

Xiang Chen, Shao-Lin Tao, Feng Gao*, Ying-Bo Li, Jian-Jiang Zhong   

  1. 1. Department of Pharmaceutical Sciences, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
    2. Key Laboratory of Microbial Metabolism, Ministry of Education, College of Life Science & Biotechnology, Shanghai Jiaotong University, Shanghai 200240, China
  • Received:2009-12-28 Revised:2010-03-15 Online:2010-05-15 Published:2010-05-15
  • Contact: Feng Gao*

摘要: 建立大鼠血浆中灵芝酸单体T的高效液相色谱测定方法, 并应用于其药动学研究。采用反相色谱柱, 检测波长为245 nm, 流动相为甲醇-水-乙酸 (95.5:4.5:0.5, v/v/v); 流速为l mL/min; 内标为丙酸睾酮。灵芝酸单体T血浆浓度在 0.05~50 μg/mL范围内线性良好 (r>0.999), 定量限为20 ng/mL, 低、中、高浓度质控样品回收率分别为97.6%, 98.4% 和103.2%, 日内、日间精密度 (以相对标准偏差表示)不超过8.2%。大鼠静脉给药主要药动学参数为: t1/2α: (5.46±1.25) min; t1/2β: (227.18±11.40) min; CL: (1.09±0.16) mL/(kg·min); AUC0–12 h: (3939.13±311.14) μg·min/mL; AUC0–∞: (4681.96±710.70) μg·min/mL, 绝对生物利用度为41.98%±2.40%。该方法快速简便、灵敏度高、定量准确, 适用于大鼠体内灵芝酸的药物动力学研究。

关键词: 灵芝酸T, 药动学, 大鼠血浆, 高效液相色谱

Abstract:

A selective and sensitive HPLC method has been developed and validated for the quantification of ganoderic acid T in rat plasma. A reverse-phase column was used with UV detection at 245 nm. The mobile phase consisted of methanol-water-acetic acid (95.5:4.5:0.5, v/v/v) run at a flow rate of 1 mL/min. Testosterone propionate was used as the internal standard. The standard curve was linear over the range of 0.05-50 μg/mL in rat plasma with a linear correlation coefficient greater than 0.999. The lower limit of quantification of this assay was 20 ng/mL. The recoveries of samples at 0.05, 2 and 40 μg/mL were 97.6%, 98.4% and 103.2%, respectively. The relative standard deviations of intra- and inter-day assay variations were less than 8.2%. The usefulness of the assay was confirmed by the successful analysis of plasma samples from a pharmacokinetics study in rats. Following a single dose of ganoderic acid T (5 mg/kg for i.v. or 14 mg/kg for p.o.), the main pharmacokinetic parameters by intravenous injection were: t1/2α: (5.46±1.25) min; t1/2β: (227.18±11.40) min; CL: (1.09±0.16) mL/(kg·min); AUC0–12 h: (3939.13±311.14) μg·min/mL; AUC0–∞: (4681.96±710.70) μg·min/mL and the absolute bioavailability was 41.98%±2.40%. This method is simple, sensitive, and accurate. It is suitable for pharmacokinetic studies of ganoderic acid in rats.

Key words: Ganoderic acid T, Pharmacokinetics, Rat plasma, HPLC

中图分类号: 

Supporting: Foundation items: Program for Shanghai Technology Innovation Action Plan, the Modernization of Chinese Medicine Special Project (Grant No. 08DZ1971900) and 111 Program of China (Grant No. B07023).
*Corresponding author. Tel.: 86-21-64252449