LC-MS法测定人血浆中雷米普利及其活性代谢产物雷米普利拉的浓度  

Determination of Ramipril and Its Active Metabolite Pamiprilat in Human Plasma by LC-MS

作　　者：郑国钢[1] 李会林[2] 申屠建中[3] 曾苏[1] 

机构地区：[1]浙江大学药学院,杭州310031 [2]浙江省药品检验所,杭州310004 [3]浙江大学医学院附属第一医院,杭州310003

出　　处：《中国现代应用药学》2007年第4期310-313,共4页Chinese Journal of Modern Applied Pharmacy

摘　　要：目的 建立LC-MS-MS法测定人血浆中雷米普利及其活性代谢产物雷米普利拉的浓度.方法 以依那普利为内标,采用甲醇-0.1%甲酸溶液（75∶25）为流动相,以Waters Atlantis C18色谱柱为分析柱,通过电喷雾电离源（ESI）,以选择离子反应监测（SRM）方式进行检测.用于定量分析的离子反应分别为m/z 417.3→234.3（雷米普利）、m/z 389.3→206.2（雷米普利拉）和m/z 377.3→234.2（依那普利）.结果 雷米普利和雷米普利拉分别在0.103～102.7 ng·mL-1和0.106～106.4 ng·mL^-1浓度范围内线性良好.最低检测限分别为0.05 ng·mL^-1和0.10 ng·mL^-1（S/N=5）.雷米普利和雷米普利拉的日内、日间精密度（RSD）均小于9%,低、中、高3个浓度的方法回收率均大于90%.结论 本法专属性强,样品处理方便,灵敏度高,适用于雷米普利临床药物动力学研究.OBJECTIVE To establish a LC-MS-MS method for the determination of ramiprilat and its active metabolite ramiprilat in the human plasma. METHODS Enalapril was used as the internal standard. Ramipril and Ramiprilat was chromatographed by using a Waters Atlantis C18 column. The mobile phase consisted of metanol- 0. 1% formic acid solution（75：25 ）. Electrospray ionization （ESI） source was applied and operated in the positivion mode. Selected reaction monitoring（SRM） mode with the transitions of m/z 417.3→234.3 ,m/z 389.3→206.2 and m/z 377.3→234.2 were used to quantify ramipril,ramiprilat and the internal standard, respectively. RESULTS The assay linearities of ramipril and ramiprilat were confirmed over the range 0. 103 - 102.7 ng · mL^-1 and 0. 106 - 106.4 ng · mL^-1 , and their detect limits of were 0.05 ng · mL^-1and 0. 10 ng· mL^-1 , respectively. The inter and intra-day precision （RSD） were less than 9% . The average recoveries were above 90%. CONCLUSION The method was proved to be robust, covenient, sensitivity and suitable for the clinical investigation of ramipril pharmacokinetics.

关 键 词：雷米普利 雷米普利拉 液相色谱-质谱联用法 血浆药物浓度 

分 类 号：R917.103[医药卫生—药物分析学] R972[医药卫生—药学]