3种常用碳青霉烯类抗生素血药浓度UPLC-MS/MS检测方法的建立  

Establishment of UPLC-MS/MS method for the determination of plasma concentration of three common carbapenem antibiotics

作　　者：秦怡 张瑞霞[2] 吕雅瑶 翁莉莉 张弋[2] QIN Yi;ZHANG Ruixia;LYU Yayao;WENG Lili;ZHANG Yi(First Central Clinical College of Tianjin Medical University,Tianjin 300192,China;Dept.of Pharmacy,Tianjin First Central Clinical Hospital,Tianjin 300192,China)

机构地区：[1]天津医科大学一中心临床学院,天津300192 [2]天津市第一中心医院药学部,天津300192

出　　处：《中国药房》2024年第3期343-347,共5页China Pharmacy

基　　金：中国研究型医院学会药物评价专委会临床重点药品的使用监测和评价研究专项(No.Y2021FH-YWPJ01-107);吴阶平医学基金会临床科研专项资助基金(No.320.6750.2020-11-32)。

摘　　要：目的 建立3种临床常用碳青霉烯类抗生素——厄他培南(ETP)、亚胺培南(IPM)、美罗培南(MEM)血药浓度检测的超高效液相色谱-质谱联用(UPLC-MS/MS)法。方法 血浆样品经甲醇沉淀蛋白后,以3种抗生素的稳定性同位素(ETP-D4、IPMD4、MEM-D6)为内标,采用ACQUITY UPLC BEH C18(2.1 mm×50 mm,1.7μm)色谱柱分离;流动相为98%乙腈+2%水+0.1%甲酸和98%水+2%乙腈+0.1%甲酸,梯度洗脱;流速为0.3 mL/min;柱温为40℃;采用正离子、多反应监测模式进行扫描分析。结果该方法专属性良好,在ETP、IPM、MEM 0.2~200、0.1~100、0.1~100μg/mL范围内线性良好(r2≥0.993),批内、批间精密度和准确度良好(RE均≤5.14%,RSD均≤11.15%),基质效应、提取回收率较一致(RSD≤12.99%)。结论 本实验建立了一种可以同时定量ETP、IPM、MEM血药浓度的UPLC-MS/MS法,该方法样品前处理简单、检测时间短、所需样品量少,可满足临床需求。OBJECTIVE To establish a UPLC-MS/MS method for the determination of plasma concentration of three carbapenem antibiotics,i.e.ertapenem(ETP),imipenem(IPM)and meropenem(MEM).METHODS After protein precipitation with methanol,the plasma samples were separated by ACQUITY UPLC BEH C18 column(2.1 mm×50 mm,1.7μm)using stable isotopes of three antibiotics(ETP-D4,IPM-D4,MEM-D6)as the internal standard.The mobile phases were 98%acetonitrile+2%water+0.1%formic acid and 98%water+2%acetonitrile+0.1%formic acid,by gradient elution.The flow rate was 0.3 mL/min and the column temperature was 40℃.Scanning analysis was performed in the positive ion and multiple reaction monitoring mode.RESULTS The method had good specificity,good linearity(r2≥0.993)in the range of 0.2-200,0.1-100 and 0.1-100μg/mL of ETP,IPM and MEM,and good intra-batch and inter-batch precision and accuracy(all RE≤5.14%,all RSD≤11.15%),the matrix effect and extraction recovery were consistent(RSD≤12.99%).CONCLUSIONS This study establishes the UPLC-MS/MS method to simultaneously quantify the plasma concentration of ETP,IPM and MEM.The method has the advantages of simple pretreatment,short detection time and small sample quantity to meet clinical requirement.

关 键 词：碳青霉烯类抗生素 超高效液相色谱-质谱联用 血药浓度 厄他培南 亚胺培南 美罗培南 

分 类 号：R917[医药卫生—药物分析学] R978.1[医药卫生—药学]