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中国临床药理学与治疗学 ›› 2005, Vol. 10 ›› Issue (7): 734-737.

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HPLC-MS 法测定犬血浆中三七皂苷R1的血药浓度及其药代动力学

茅向军1, 孙建国, 吕天, 王广基, 盛龙生2, 刘文英1   

  1. 中国药科大学药物代谢研究中心,1药物分析教研室,2分析测试中心, 南京210009, 江苏
  • 收稿日期:2005-04-30 修回日期:2005-06-21 出版日期:2005-07-26 发布日期:2020-11-10
  • 通讯作者: 王广基, 男, 教授, 博士生导师, 研究方向:药代动力学。Tel:025-83271544 E-mail: gjwang@cpu.edu.cn
  • 作者简介:茅向军, 男, 博士研究生, 研究方向:药物分析和药代动力学。Tel:025-85391035 E-mail: mxjun108@sina.com.cn
  • 基金资助:
    国家863 计划资助项目(NO2003AA2Z347A); 江苏省药物代谢动力学重点实验室资助项目(NOBM2001201); 江苏省自然科学基金(NOBZ2004042)

Pharmacokinetics of notoginsenoside R1 in Beagle dogs by LC-MS

MAO Xiang-jun1, SUN Jian-guo, LV Tian, WANG Guang-ji, SHENG Long-sheng2, LIU Weng-ying1   

  1. Center for Drug Metabolism and Pharmacokinetics, 1Department of Pharmaceutic Analysis, 2Center for Instrumental Analysis, China Pharmaceutical University, Nanjing 210009, Jiangsu, China
  • Received:2005-04-30 Revised:2005-06-21 Online:2005-07-26 Published:2020-11-10

摘要: 目的: 建立用于测定三七皂苷R1 血药浓度的液相色谱-质谱联用分析方法, 并研究三七皂苷R1在犬体内的药代动力学。方法: Beagle 犬6 只iv0.7131 mg·kg-1 三七皂苷R1后采集系列血样, 利用LC-MS 联用系统测定血浆药物浓度, 并用3P97 软件拟合求算药代动力学参数。结果: 三七皂苷R1 浓度在5.0 ~ 2 000 μg·L-1 内, 线性关系良好(γ =0.9996) 。绝对回收率高于90 %, 日内、日间RSD 均小于15 %, 符合生物样品分析要求。6 只Beagle 犬iv 0.7131 mg·kg-1 三七皂苷R1 后的血药浓度-时间曲线符合二室模型, 其分布和消除相的半衰期分别为38.59 min 和230.06 min 。曲线下面积(AUC) 、中央室分布容积(V) 和血浆清除率(CL) 分别为67353.75 mg·min·ml-1, 3.53 L·kg-1 和0.1068L·kg-1·min-1结论: 建立的LC-MS 联用方法专属性强, 灵敏度高, 可用于三七皂苷R1的体内定量分析。

关键词: 三七皂苷R1, 液相色谱-质谱, 血药浓度测定, 药代动力学, Beagle犬

Abstract: AIM: To establish an analytical method for determination of notoginsenoside R1 concentration in plasma and to study its pharmacokinetic profile in dogs. METHODS: Six dogs were intravenously administration of 0.7131 mg·kg-1 notoginsenoside R1. Blood samples were collected at various time-points after drug administration. Analytical method based on liquid chromatography- mass spectrometry(LC-MS) was established to determine the plasma concentration of notoginsenoside R1. Pharmacokinetic evaluation was carried out using the 3P97 program. RESULTS: The calibration curves were linear over the concentration ranged from 5 to 2 000 μg·L-1 (γ =0.9996). The intra-day and inter-day precisions were generally good (<15 %) at low, medium and high concentrations. The overall recovery was more than 90 %. Six dogs were intravenously administration of 0.7131 mg·kg-1 notoginsenoside R1, and an open two compartment model best described the concentration-time profiles for notoginsenoside R1. The half-lifes for the rapid and slow distribution phase (T1/2α and T1/2β) were 38.59 and 230.06 min, respectively. The total area under the plasma concentration /time curve (AUC), the volume of the central compartment (V) and plasma clearance(CL) were 67353.75 mg·min·ml-1, 3.53 L·kg-1 and 0.1068 L·kg-1 ·min-1, respectively. CONCLUSION: The analytical method is sensitive, specific, rapid and reproducible, and it is suitable for pharmacokinetic studies of notoginsenoside R1.

Key words: notoginsenoside R1, liquid chromatography-mass spectrometry, pharmacokinetics, Beagle dogs

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