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高效液相色谱法测定大鼠组织及血浆中9-硝基喜树碱含量 被引量:18

Determination of 9-nitrocamptothecin in rat plasma and tissues by high performance liquid chromatography
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摘要 目的 建立高效液相色谱法测定大鼠血浆及组织样品中 9 硝基喜树碱 ,并研究其在大鼠体内的分布特点。方法 血浆及组织样品经液 液萃取后 ,分别以乙腈 水 甲酸 ( 3 5∶65∶2 )或乙腈 水 甲酸 ( 3 0∶70∶2 )为流动相 ,使用HypersilBDSC1 8色谱柱进行分离 ,检测波长为UV 3 70nm。结果 该法测定 9 硝基喜树碱在血浆中线性范围为 2 5~160 0 μg·L- 1 。药物iv后在大鼠体内广泛分布 ,肺中浓度最高 ,并在肺和肝中有蓄积现象。ig给药后 ,药物在胃中浓度最高 ,肠组织次之 ,大多数组织中药物浓度较低。结论 该法操作简便、快速 ,适用于 9 Aim To develop a sensitive, specific and accurate method for quantifying 9 nitrocamptothecin in rat plasma and tissues and to study the distribution of 9 nitrocamptothecin in rat tissues. Methods Plasma and tissue samples were prepared based on a simple liquid liquid extraction and separation through a Hypersil BDS C 18 column. The mobile phase for plasma samples and tissue samples consisted of a mixture of acetonitrile water formic acid (35∶65∶2) and a mixture of acetonitrile water formic acid (30∶70∶2), respectively. The UV detector was set at 370 nm. Results A linear calibration curve of 9 nitrocamptothecin in plasma was obtained in the concentration range of 25- 1 600 μg·L -1 , and the quantitation limit of plasma and tissues was 25 μg·L -1 . A linear range of concentrations for 9 nitrocamptothecin in heart, lung, spleen, stomach, fat, womb, and ovary was 10- 1 000 ng·g -1 , and the quantitation limit was 10 ng·g -1 . A linear range of concentrations for 9 nitrocamptothecin in brain, kidney, liver, intestine, smooth muscle, skeletal muscle, and tectical was 5-500 ng·g -1 , and the quantitation limit was 5 ng·g -1 . The intra and inter run precision was measured to be below 11%. The inter run accuracy was less than 5% for the analyte. After iv administration of 9 nitrocamptothecin, the drug was distributed extensively in rat in vivo . The concentration in lung was the highest, and the drug was accumulated in lung and liver. Following ig administration, the concentration in stomach was higher than that in other organs. Conclusion The method is shown to be accurate and convenient, and suitable for preclinical pharmacokinetic studies of 9 nitrocamptothecin.
作者 李柯 钟大放
出处 《药学学报》 CAS CSCD 北大核心 2003年第2期124-128,共5页 Acta Pharmaceutica Sinica
基金 国家自然科学基金资助项目 ( 39930 180 )
关键词 高效液相色谱法 测定 大鼠 组织 血浆 9-硝基喜树碱 抗肿瘤药 nitrocamptothecin HPLC tissue distribution plasma
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