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中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (12): 1361-1364.

• 研究原著 • 上一篇    下一篇

LC-MS 法测定Beagle 犬血浆中苦参碱及其药代动力学

王素军, 王广基, 李晓天, 马仁玲1, 盛龙生1, 孙建国, 谢海棠   

  1. 中国药科大学药物代谢研究中心, 1分析测试中心, 南京 210038, 江苏
  • 收稿日期:2004-09-15 修回日期:2004-10-28 出版日期:2004-12-26 发布日期:2020-11-19
  • 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:王素军, 男, 博士研究生, 研究方向:药代动力学。Tel:025-85391035 E-mail:wsj7272@sina.com
  • 基金资助:
    国家863 计划基金项目(No2003AA2Z347A); 国际合作项目(NoBZ2004042);江苏省药物代谢动力学重点实验室项目(NoBM2001201)

Pharmacokinetics of matrine in Beagle dogs by LC-MS

WANG Su-Jun, WANG Guang-Ji, LI Xiao-Tian, MA Ren-Ling1, SHENG Long-Sheng1, SUN Jian-Guo, XIE Hai-Tang   

  1. Center for Drug Metabolism and Pharmacokinetics, 1Center for Instrumental Analysis, China Pharmaceutical University, Nanjing 210038, Jiangsu, China
  • Received:2004-09-15 Revised:2004-10-28 Online:2004-12-26 Published:2020-11-19

摘要: 目的: 建立Beagle 犬血浆中苦参碱的LC-MS测定法, 测定其药物动力学及绝对生物利用度。方法: 采用Lichrospher C18 柱, 250 mm×4.6 mm(ID),5 μm, 柱温:25 ℃;流动相:10 mmol·L-1醋酸胺水溶液∶甲醇(25 ∶75), 流速:1 ml·min-1 。电喷雾离子化(ESI) 方式, 采用选择性离子检测, 检测离子为正离子, 苦参碱的离子是[M+H] +, m/z 249.2 。结果: 苦参碱在2~5 000 μg·L-1的范围内呈良好的线性关系(r=0.9975), 最低检出限达0.3 μg·L-1。日内和日间误差均小于4.5 %, 方法回收率大于96.6 %;药-时数据符合二室模型, Cmax 为3821±705 μg·L-1, Tmax为0.4±0.1 h, T1/2β为11.2±2.1 h,AUC0→∞为7446±1456 μg·h·L-1, 绝对生物利用度为(60.1±19.0) %。结论: 该法灵敏、快速、简单, 专属性强, 苦参碱在Beagle 犬体内有较高的绝对生物利用度。

关键词: 苦参碱, 药代动力学, 液相色谱 质谱联用, Beagle 犬, 绝对生物利用度

Abstract: AIM: To establish LC-MS method in the determination of matrine in plasma of Beagle dogs and to investigate its absolute bioavailability.METHODS: Lichrospher C18 column was used as the analytical column and maintained at 25 ℃, 250 mm×4.6 mm (ID), and 5 μm.The mobile phase was consisted of 10 mmol·L-1ammonium acetate and methanol (25 ∶75, v ∶v).Flow rate was 1 ml·min-1.Electrospray ionization (ESI) was carried out.The ESI ion source was set in positive ion polarity mode.The selective ion monitoring (SIM) was set at m z 249.2 for matrine.RESULTS: The linearity of matrine ranged from 2 to 5 000 μg·L-1(r=0.9975) and the detection limits of it was 0.3 μg·L-1.The RSD of within day and between day was less than 4.5 %.The recovery of this method was more than 96.6 %.The disposition was conformed to a two-compartment model.The Cmax, Tmax, T1/2β, AUC0→∞ and absolute bioavailability of matrine were 3821±705 μg·L-1, 0.4±0.1 h, 11.2±2.1 h, 7446±1456 μg·L-1·h and (60.1±19.0) %, respectively.CONCLUSION: This study provides a highly sensitive, rapid, simple and special method for determining concentrations of matrine in plasma of Beagle dogs.Matrine shows higher absolute bioavailability in Beagle dogs.

Key words: matrine, pharmacokinetics, absolute bioavailability, LC-MS, Beagle dogs

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