HPLC法测定大鼠组织中的桂利嗪
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HPLC in determination of tissue distribution of cinnarizine in rats
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    摘要:

    目的:建立大鼠组织中桂利嗪的HPLC测定法,用于小剂量尾静脉注射给药后测定桂利嗪在大鼠组织中分布。方法:组织样品加NaOH碱化,以甲基叔丁基醚提取,采用Hypersil C18 柱,甲醇-水- 冰醋酸-三乙胺(70300.60.4)为流动相,254 nm波长处检测,测定了尾静脉给药2 mg/kg桂利嗪注射液后在SD大鼠心、肝、脾、肺、肾、胃、小肠、脑、脂肪、睾丸等10个组织脏器中的分布情况。结果:肝组织样品最低检测限0.02 μg/ml,线性范围0.05~2 μg/ml,小肠组织样品最低检测限0.02 μg /ml,线性范围0.05~1 μg/ml,符合生物样品分析要求。桂利嗪广泛地分布于大鼠的多个组织脏器中,其中肺部浓度最高。结论:本法简便、准确、灵敏,适合桂利嗪临床前药代动力学组织分布研究。

    Abstract:

    Objective:To develop a HPLC method for the determination of tissue distribution of cinnarizine in rats. Methods: Cinnarizine (2 mg/Kg) was injected into the tail vein of rats. Tissue sample was alkalized with sodium hydroxide solution and extracted with methyl tert-butyl ether. The separation was performed on a Hypersil C18 column using methanol-water-glacial acetic acidacid-triethylamine (70300.60.4) as the mobile phase at UV 254 nm. The distribution of cinnarizine in the heart, liver, spleen, lung, kidney, stomach, small intestine, brain, fat and testes was determined. Results: The limit of detection of cinnarizine in the hepatic tissue was 0.02 μg /ml and the linear range was 0.05-1 0 μg/ml. The limit of detection in the intestine tissue was 0.02μg /ml and the linear range was 0.05-1 μg/ml, which meets the requirement for the analysis of biological samples. Cinnarizine was extensively distributed in rat body, with highest concentration found in the lung. Conclusion: Our method is easy to perform, accurate and sensitive, which makes it suitable for preclinical pharmacokinetic research of cinnarizine.

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  • 收稿日期:2007-09-03
  • 最后修改日期:2008-01-05
  • 录用日期:2008-01-14
  • 在线发布日期: 2008-03-17
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