液质联用法检测大鼠血浆中缬沙坦的浓度  

Determination of valsartan in rat plasma by liquid chromatography-tandem mass spectrometry

作　　者：闫婷婷[1,2] 刘维[1,3] 张现化[1,3] 熊歆[1,3] 张元元[1,3] 杨丽[1,3] 翟所迪[1,3] 

机构地区：[1]北京大学第三医院药剂科,北京100191 [2]北京大学药事管理与临床药学系,北京100083 [3]北京大学治疗药物监测与临床毒理中心,北京100191

出　　处：《中国临床药理学杂志》2016年第10期927-929,940,共4页The Chinese Journal of Clinical Pharmacology

基　　金：北京大学第三医院回国人员启动基金资助项目(73486-02);北京大学第三医院种子基金资助项目(84498-01)

摘　　要：目的建立检测大鼠血浆中缬沙坦浓度的液质联用方法。方法选择氯沙坦作为内标,用乙腈沉淀蛋白法处理样本。色谱柱:Agilent ZORBAX XDBC18(2.1 mm×50 mm,5μm),流动相:乙腈-0.1%甲酸水溶液,梯度洗脱,流速:0.3 m L·min^(-1),进样量:1μL,分析时间:5 min。用电喷雾离子源,多反应监测模式进行正离子检测。考察该方法的专属性、标准曲线和定量下限、精密度与回收率、基质效应、稳定性。结果缬沙坦在10~2000 ng·m L^(-1)内线性关系良好(r=0.999 0),定量下限为10 ng·m L^(-1)。血样日内及日间RSD分别为1.83%~3.83%和5.60%~8.89%,回收率为78.82%~85.98%。室温放置24h、处理后放置72 h、冻融3次及-20℃冻存1个月后样本均保持稳定。结论本方法是一种简单、快速、灵敏的检测大鼠血浆中缬沙坦浓度的方法,可满足动物实验中低剂量给药的浓度测定要求。Objective To establish a liquid chromatography-tandem mass spectrometry（ LC-MS /MS） method to determine valsartan in rat plasma.Methods Samples were detected using electrospray ionization（ ESI）source in positive mode.Losartan was chosen as internal standards,plasma samples were precipitated by acetonitrile.Agilent ZORBAX XDB-C18（ 2.1mm × 50 mm,5 μm） was used.Mobile phase was acetonitrile-0.1% acetic acid,gradient elution at a flow rate of 0.3 m L·min-（-1）.Injection volume was 1 μL,and run time was 5 min.The method was validated by investigating its specificity,linearities and limit of detection,precision,extraction recovery,stability and matrix effect.Results A good linearity was obtained over the range of 10-2000 ng·m L^-1,with a lower limit of quantitation at10 ng·m L^-1.The relative standard deviation（ RSD） of intra-day and inter-day were 1.83%-3.83%,5.60%-8.89%,respectively.The recovery was 78.82%-85.98%.All samples were stable after being stored 24 h at room temperature,being stored 72 h after preparation,three freeze-thaw cycles and being cryopreserved 1 month at-20 ℃.Conclusion The developed LC-MS /MS method was simple,rapid,and sensitive,it can be applied to the analysis of valsartan in rat plasma at low pharmacology concentration range.

关 键 词：缬沙坦 氯沙坦 液质联用 

分 类 号：R972.6[医药卫生—药品]