高效液相色谱法测定人血浆中霉酚酸酯及其活性代谢物霉酚酸的浓度  

HPLC Determination of Mycophenolate Mofetil and Its Active Metabolite Mycophenolic Acid in Human Plasma

作　　者：余自成[1] 蔡卫民[1] 徐达[1] 王祥慧[1] 

机构地区：[1]上海第二医科大学附属瑞金医院临床药理研究室,上海200025

出　　处：《药物分析杂志》2005年第4期381-384,共4页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立快速测定人血浆中霉酚酸酯(mycophenolate mofetil,MMF)及其活性代谢物霉酚酸(mycophenolic acid,MPA)浓度的高效液相色谱方法。方法:色谱柱:μBondapak C_(18)(10μm,3.9mm×300mm),流动相:40mmol·L^(-1)TBA-乙腈(65:35),流速:1.0mL·min^(-1),紫外检测波长:254nm,柱温:45℃,血浆样品用2.5倍体积的乙腈沉淀蛋白后直接进样,按内标法定量,内标物选用酰胺咪嗪。结果:MMF 和 MPA 的线性范围分别在:0.2-37.5μg·mL^(-1)和0.56-35.0μg·mL^(-1),最低检测浓度分别为0.10和0.50μg·mL^(-1)。MMF 测定的平均回收率为98.00%-101.0%,日内、日间精密度 RSD 为2.9%-6.7%,MPA 测定的平均回收率为97.88%-101.8%,日内、日间精密度 RSD 分别小于6%和8%。结论:本方法简便快速、定量准确,可用于 MMF 临床药动学研究,也可用于 MPA 血药浓度的常规监测。Objective:To establish a rapid and feasible HPLC method for the determination of mycophenolate mofetil (MMF) and its active metabolite mycophenolic acid(MPA) in human plasma.Methods:The plasma sample(0.2 mL) was deproteinized with 0.5 mL of acetonitrile and then analyzed on an μBondapak C_(18) (3.9 mm×300mm)col- umn with a 40 mmol·L^(-1) tetrabutyl ammonium bromide (TBA)-acetonitrile (65:35) mobile phase.The flow rate was 1.0 mL·min^(-1),the eluent was detected at 254 nm,the MMF and MPA concentration were obtained by internal standard method,carbamazepine was used as an internal standard.Results:Calibration curves were linear over a concentration range of 0.2-37.5μg·mL^(-1) for MMF,and 0.5-35.0μg·mL^(-1) for MPA.Average recoveries were 98.00%-101.0% for MMF,97.88%-101.8% for MPA.Within-day precision of determination were less than 6% for both MMF and MPA,between-day precision were less than 8%.Conclusion:This method is simple, quick,accurate and can be used for the monitoring of the plasma concentration of MPA routinely and for the study on the clinical pharmacokinetics of MMF.

关 键 词：活性代谢物 霉酚酸酯 高效液相色谱法 人血浆 平均回收率 液相色谱方法 紫外检测波长 药动学研究 MPA MMF 快速测定 acid 直接进样 沉淀蛋白 血浆样品 酰胺咪嗪 线性范围 检测浓度 血药浓度 RSD 精密度 色谱柱 流动相 内标法 

分 类 号：R969.1[医药卫生—药理学] R593.242[医药卫生—药学]