LC-MS/MS法测定大鼠血浆中托拉塞米浓度及其药代动力学研究  

Determination of torasemide in rat plasma by LC-MS/MS and its pharmacokinetic study

作　　者：李晓波 徐志勇[2] 刘瑞东[2] 茹丽 袁征[2] 宋健平[1] 徐勤 LI Xiao-bo;XU Zhi-yong;LIU Rui-dong;RU Li;YUAN Zheng;SONG Jian-ping;XU Qin(Artemisinin Research Center,Guangzhou University of Chinese Medicine,Guangzhou 510000,Guangdong Province,China;Institute of Science and Technology,Guangzhou University of Chinese Medicine,Guangzhou 510000,Guangdong Province,China)

机构地区：[1]广州中医药大学青蒿研究中心,广东广州510000 [2]广州中医药大学科技园,广东广州510000

出　　处：《中国临床药理学杂志》2020年第15期2306-2309,共4页The Chinese Journal of Clinical Pharmacology

基　　金：“重大新药创制”科技重大专项基金资助项目(2018ZX09303008);国家自然科学基金面上基金资助项目(81873218);广州市科技计划资助项目(201807010007)。

摘　　要：目的建立一种快速可靠的测定大鼠血浆中托拉塞米浓度的高效液相色谱-串联质谱检测方法,并进行药代动力学研究。方法以甲苯磺丁脲为内标,血浆样品用甲醇直接沉淀蛋白,用Agela Innoval ODS-2色谱柱(4.6 mm×150.0 mm,5μm),流速为0.7 mL·min^-1,流动相为甲醇-5 mmol·L^-1醋酸铵水(80∶20)。质谱用电喷雾离子源,负离子模式,多重反应监测模式进行检测。考察该方法的专属性、标准曲线与定量下限、精密度与回收率等。结果托拉塞米在20.00~2.00×104 ng·mL^-1内线性关系良好,定量下限为20 ng·mL^-1,批内、批间精密度和准确度均小于10%,方法学考察均符合生物样品分析的要求。结论本方法快速灵敏、准确可靠,适用于大鼠体内托拉塞米的血药浓度测定。Objective To develop a rapid and reliable high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for the determination of torasemide in rat plasma,and to study its pharmacokinetics.Methods Tolbutamide was used as the internal standard.Plasma samples were pretreated by protein precipitation with methanol.Chromatographic separation was carried out on Agela Innoval ODS-2 column(4.6 mm×150.0 mm,5μm)by isocratic elution with methanol-5 mmol·L^-1 ammonium acetate(80∶20)at a flow rate of 0.7 mL·min^-1.Detection and quantification were performed using mass spectrometry under the multiple reaction monitoring modes with negative electrospray ionization.The specificity,standard curve and lower limit of quantification,precision and recovery rate of the method were investigated.Results A good linear relationship of torasemide was obtained in the concentration range from 20.00 ng·mL^-1 to 2.00×10^4 ng·mL^-1 and the lower limit of quantitation was 20 ng·mL^-1.The intra-and inter-assay precisions and accuracies of the methods were less than 10%.The method validation was subjected to the requirements of biological sample analysis.Conclusion This method is rapid,sensitive,accurate and reliable,which is suitable for the measurement of plasma torasemide concentration in rats.

关 键 词：托拉塞米 高效液相色谱-串联质谱 SD大鼠 药代动力学 

分 类 号：R983.1[医药卫生—药品]