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氧化苦参碱在犬体内的药动学

Pharmacokinetics of oxymatrine in beagle dogs

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【作者】 王素军王广基李晓天孙建国李昊谢海棠马仁玲

【Author】 WANG Su-jun~1,~ WANG Guang-ji~1 ,LI Xiao-tian~1,SUN Jian-guo~1,LI Hao~1 ,XIE Hai-tang~1,MA Ren-ling~2(1.Center of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Jiangsu Nanjing 210038,China;2.Center for Instrumental Analysis,China Pharmaceutical University,Jiangsu Nanjing 210038,China)

【机构】 中国药科大学药物代谢研究中心中国药科大学分析测试中心 江苏南京210038江苏南京210038江苏南京210038

【摘要】 目的:建立beagle犬血浆中氧化苦参碱的LCMS测定法,测定其灌胃后在beagle犬体内的药动学。方法:采用LichrospherC18柱(250mm×4.6mm,5μm),柱温:25℃。流动相为10mmol·L-1醋酸铵水溶液甲醇(25∶75),流速:1mL·min-1;电喷雾离子化(ESI)方式,采用选择性离子检测法,检测离子为正离子,氧化苦参碱的离子为[m/z+H]+265.1,内标非那雄胺的离子是[m/z+H]+373.3。结果:氧化苦参碱在2~5000μg·L-1的范围内呈良好的线性关系(r=0.9990),最低检出限达0.6μg·L-1,日内和日间误差均小于4.2%,萃取回收率大于90%;氧化苦参碱的药时数据符合二室模型,Cmax为(2418.3±970.8)μg·L-1,tmax为(1.0±0.3)h,t1/2β为(5.5±1.6)h,AUC0→∝为(6117.4±1080.2)μg·L-1·h。结论:该法灵敏、简单,专属性强,可用于犬血浆中氧化苦参碱的测定。

【Abstract】 OBJECTIVE To establish LC-MS method in the determination of oxymatrine in plasma and investigate its pharmacokinetics in beagle dogs.METHODS Lichrospher C18 column was used as the analytical column maintained at 25 ℃ (250 mm×4.6 mm,5 μm).The mobile phase consisted of 10 mmol·L-1 CH3COONH4 -CH3OH (25∶75). Flow rate was 1 mL·min-1.Electrospray ionization(ESI)was carried out. The ESI ion source was set in positive ion polasity mode.The selective ion monitoring (SIM) was set at m/z 265.1 for oxymatrine.RESULTS The linearity of oxymatrine ranged from 2 to 5 000 μg·L-1(r=0.999 0).The detection limits of oxymatrine was 0.6 μg·L-1.The RSD(%) of within day and between day was less than 4.2%.The recovery was more than 90%.The disposition was conformed to a two-compartment model.TheCmax,Tmax,T1/2β,AUC0→∝ of oxymatrine were (2 418.3±970.8) μg·L-1, (1.0±0.3) h,(5.5±1.6) h,(6 117.4±1 080.2) μg·L-1·h.CONCLUSION This method is highly sensitive,rapid,simple and specific enough for determining concentrations of oxymatrine in plasma of beagle dogs.

【关键词】 氧化苦参碱药动学液相色谱质谱联用
【Key words】 oxymatrinephamacokineticsLC-MS
【基金】 国家863计划(编号:2003AA2Z347A);国际合作项目(编号:BZ2004042)
  • 【文献出处】 中国医院药学杂志 ,Chinese Journal of Hospital Pharmacy , 编辑部邮箱 ,2005年07期
  • 【分类号】R969.1
  • 【被引频次】13
  • 【下载频次】398
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