| 摘要: |
| 目的:建立LC/MS/MS法测定大鼠血﹑尿液和胆汁中氯沙坦的浓度,研究氯沙坦在大鼠体内的药物动力学特点。方法:大鼠血浆样品采用沉淀蛋白作为前处理方法,尿液和胆汁采用液-液萃取方法进行前处理,进样检测。色谱柱为Agela Venusil MP-C18 2.1 mm×50 mm,粒径5 μm;流动相A为0.1％甲酸,流动相B为0.1％甲酸（溶剂为乙腈）。采用梯度洗脱:流动相B在1.5 min内从20%到95%,流速0.35 ml/min,进样量为10 μl,质谱仪检测,离子源为ESI源。结果:氯沙坦在血、尿液和胆汁中的线性范围为1~1 000 μg/L,线性良好(r>0.99),平均相对回收率>80.0%,日内和日间精密度均小于15％。结论:该检测方法操作方便,结果准确,专属性强,可用于血﹑尿液和胆汁中氯沙坦药物含量的测定。 |
| 关键词: 氯沙坦 血浆 胆汁 尿 液质联用 |
| DOI：10.3724/SP.J.1008.2008.01091 |
| 投稿时间：2008-02-20修订日期：2008-06-16 |
| 基金项目: |
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| Determination of losartan concentrations in rat plasma,urine and bile by liquid chromatography-tandem mass spectrometry |
| JIANG Hua-fang1,2,DUAN Ming-yu2,XING Jin-song2,ZHAO Ning2,Agela Wong2,FAN Guo-rong1* |
| (1.Department of Drug Analysis,School of Pharmacy,Second Military Medical University,Shanghai 200433,China*2.WuXi PharmaTech Co.,LTD,Shanghai 200131) |
| Abstract: |
| Objective:To establish a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for determination of the losartan concentrations in rat plasma,urine and bile．Methods: The method was based on a protein precipitation procedure for rat plasma and liquid-liquid extraction for rat urine and bile,then the diluted extract was analyzed by LC/MS/MS using turbo ion spray (TIS) positive ion mode.Chromatography was performed on an Agela Venusil MP-C18 column (5 μm particle,2.1 mm×50 mm) by gradient elution.Mobile phase A was 0.1% formic acid in water and mobile phase B was 0.1% formic acid in acetonitrile.The mobile phase B increased from 20% to 95% within 1.5 min,with the flow rate being 0.35 ml/min and the feeding rate being 10 μl.Electrospray ionization (ESI) ion source was used.Results: The linear range of losartan was 1-1 000 μg/L in the plasma,urine and bile of rats (r>0.99).The mean relative recovery rate was higher than 80.0%;RSD values of intra-day and inter-day were both less than 15%.Conclusion: The present method is easy to perform,accurate,and specific; it can be used for determination of losartan concentration in rat plasma,urine and bile． |
| Key words: losartan plasma bile urine LC/MS/MS |
