双内标高效液相色谱-质谱联用法测定人血浆中美罗培南浓度  

Determination of meropenem in human plasma by HPLC-MS/MS with two internal standards

作　　者：刘洪川[1] 李鹏飞[1] 胡婷 杜萍[1] 韩菲菲[1] 刘丽宏[1] LIU Hong-chuan;LI Peng-fei;HU Ting;DU Ping;HAN Fei-fei;LIU Li-hong(Department of Pharmacy,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020,China)

机构地区：[1]首都医科大学附属北京朝阳医院药事部,北京100020

出　　处：《中国临床药理学杂志》2020年第17期2706-2709,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的建立快速测定人血浆中美罗培南质量浓度的方法。方法以乙腈为沉淀剂,经蛋白沉淀法处理,进高效液相串联质谱系统(HPLC-MS/MS)分析,色谱柱:Waters XBrige C18(2.1 mm×50 mm,3.5μm),流动相:乙腈(含0.1%甲酸)-水(含0.1%甲酸),流速:0.4 mL·min^-1,柱温:40℃,进样量:3μL,电喷雾电离,用多反应监测模式,定量分析离子对分别为m/z 384.3→140.6(美罗培南)、237.1→194.1(内标卡马西平),285.1→193.0(内标地西泮)。结果以卡马西平为内标标准曲线方程为y=2.95×10^-2x+1.46×10^-2(r=0.9972),以地西泮为内标标准曲线方程为y=0.19x+5.21×10^-3(r=0.9974)。线性范围为0.20~50.00μg·mL^-1。批间和批内精密度均在4.46%~9.52%,准确度均在94.12%~110.00%,平均提取回收率均在92.50%~104.00%,稳定性好。结论本方法样品处理简便,灵敏度高,专属性强,适用于美罗培南的血药浓度监测。Objective To develop a rapid method for determining the concentration of meropenem in human plasma.Methods The clinical plasma samples were treated by protein precipitation using acetonitrile as a precipitant,and then were determined by high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).The column was Waters XBrige C18(2.1 mm×50 mm,3.5μm),and the mobile phase was acetonitrile(0.1%formic acid)-water(0.1%formic acid).The flow rate was 0.4 mL·min^-1,the column temperature was 40℃,the injection volume was 3μL,and the electrospray ionization source was used.The multi-reaction monitoring mode was used to quantitatively analyze the ionization pairs as m/z 384.3→140.6(meropenem),237.1→194.1(carbamazepine),285.1→193.0(diazepam).Results The standard curve using carbamazepine as internal standard was y=2.95×10^-2x+1.46×10^-2(r=0.9972),the standard curve using diazepam as internal standard was y=0.19x+5.21×10^-3(r=0.9974),the linear range was 0.20-50.00μg·mL^-1.The inter-assay and intra-assay precision were between 4.46%-9.52%.The accuracy were between 94.12%-110.00%,and average extraction recoveries were between 92.50%-104.00%,and the stability was good.Conclusion The method was simple,sensitivity as well as specificity,suitable for monitoring the concentrations of meropenem in human plasma.

关 键 词：美罗培南 高效液相色谱-质谱联用法 血药浓度 治疗药物监测 

分 类 号：R97[医药卫生—药品]