LC-MS法测定人血浆中赖诺普利样品前处理方法改进  

Improved LC-MS method in pretreatment for the determination of lisinopril in human plasma and its application

作　　者：黄艳[1] 吴月[1] 郭晓烽[1] 吴飞[1] 丁黎[1] 文爱东[2] 杨林[2] 

机构地区：[1]中国药科大学药物分析教研室,南京210009 [2]第四军医大学西京医院国家药品临床研究基地Ⅰ期临床试验研究室,西安710032

出　　处：《药学与临床研究》2008年第2期104-107,共4页Pharmaceutical and Clinical Research

摘　　要：目的：改进人血浆中赖诺普利的LC-MS测定法。方法：通过对样品前处理方法的改进，减少样品对离子源的污染和血浆内源性物质对待测物色谱峰的干扰；通过对复溶样品所用溶液的pH值的调整，改善色谱峰形；通过提高色谱柱温度，提高传质速率，改善色谱峰形。色谱柱为SepaxGP-C18（2．1mm×150mm，5μm）柱，流动相为20mmol·L^-1醋酸铵（含0．1％甲酸）-甲醇（75：25，v／v），内标为甲硝唑，检测仪器为Agilent1100LC-MSD，离子源为ESI，检测离子为m／z 406.3（赖诺普利）、m／z 172.1（内标），裂解电压为150V。结果：赖诺普利与内标的峰形良好，色谱图中杂峰较少，在2—300ng·mL^-1浓度范围内赖诺普利与内标峰面积比值与浓度线性关系良好，最低定量限为2ng·mL^-1。本法提取回收率为91．6％～96.4％，批内和批间的精密度均小于15％。结论：该方法灵敏度高，无杂质干扰，分析速度快，可以应用于临床血药浓度的测定和药代动力学研究。Objective： To develop a LC-MS method for the determination of lisinopril concentration in human plasma. Methods：After being deproteinated by methanol, plasma samples were separated by LC-MS on Sepax GP-C18 column with mobile phase consisting of 20 mmol·L^-1 ammonium acetate （containing 0.1% formic acid） water solution - methanol （75： 25, v/v） and metronidazole being used as the internal standard. The analytes were ionized in the electro spray ionization interface of the mass spectrometer and detected in the selected ion monitoring （SIM） mode using target ions at m/z 406.3 for lisinopril and m/z 172.1 for the internal standard. The fragmental voltage was 150 V. Results： The calibration curve was linear over the range of 2 ～ 300 ng·mL^- 1 with 2 ng·mL^- 1 of the limit of quantification for lisinopril in plasma. The intra-batch and inter-batch precision were less than 15 % and accuracy ranged from 91.6% to 96.4%. Conclusion ： The developed method is suitable for phar- macokinetic study of lisinopril in human plasma.

关 键 词：赖诺普利 LC-MS 药代动力学 

分 类 号：R927.2[医药卫生—药学]