基于液相色谱串联质谱法的人血清中亚胺培南、美罗培南、万古霉素和替考拉宁的含量测定分析  

Content Determination and Analysis of Imipenem,Meropenem,Vancomycin and Teicoplanin in Human Serum Based on LC-MS/MS

作　　者：王月园 项铮 屈昱晨 樊锴 苏存锦[1] WANG Yue-yuan;XIANG Zheng;QU Yu-chen;FAN Kai;SU Cun-jin(The Second Affiliated Hospital of Soochow University,Suzhou Jiangsu 215000,China)

机构地区：[1]苏州大学附属第二医院,江苏苏州215000

出　　处：《抗感染药学》2024年第1期14-18,共5页Anti-infection Pharmacy

基　　金：苏州大学附属第二医院科研预研基金(编号:SDFEYQN2023);江苏省药学会—奥赛康药学基金项目(编号:A202118)。

摘　　要：目的:基于液相色谱串联质谱法(liquid chromatography-tandem mass spectrometry,LC-MS/MS),建立同时快速测定人血清中亚胺培南、美罗培南、万古霉素和替考拉宁含量的方法,为临床感染患者的治疗药物监测提供参考。方法:采用Agilent 1260系列液相色谱仪和API 4000三重串联四级杆质谱仪,以Phenomenex KINETEX XB-C18(2.6μm,3×50 mm)为色谱柱,以0.1%甲酸-水和纯乙腈为流动相,以电喷雾离子源、多反应离子监测结合正离子模式作为质谱条件,建立同时快速测定人血清中亚胺培南、美罗培南、万古霉素和替考拉宁4中抗菌药物含量的方法。结果:测定结果显示,4种抗菌药物和2种内标物质在保留时间处均未出现干扰峰;4种抗菌药物在各自的浓度范围内线性关系良好,其相关系数(r^(2))均大于0.99,其最低定量限的S/N均大于10;精密度和准确度检测结果显示,4种抗菌药物测定结果的日间和日内相对标准偏差(relative standard deviation,RSD)均小于10.00%,而其相对误差(relative error,RE)则均在±10.00%以内;4种抗菌药物测定结果的回收率均在85.00%~115.00%之间;稳定性考察显示,在不同温度和放置时间条件下,4种抗菌药物测定结果的RE则均在±10.00%以内。结论:LC-MS/MS可以同时快速测定血清中亚胺培南、美罗培南、万古霉素和替考拉宁4种抗菌药物的含量,且具有精密度和准确度高、稳定性强的特点,因而可以为临床治疗药物监测提供较好支撑。Objective:To establish a method for simultaneous and rapid determination of imipenem,meropenem,vancomycin and teicoplanin in human serum based on liquid chromatography-tandem mass spectrometry(LC-MS/MS),and provide reference for the therapeutic drug monitoring in clinically infected patients.Methods:By using Agilent 1260 series liquid chromatograph and API 4000 triple tandem quadrupole mass spectrometer,Phenomenex KINETEX XB-C18(2.6μm,3×50 mm)as the chromatographic column,0.1%formic acid-water and pure acetonitrile as the mobile phase,electrospray ionization(ESI),multiple reaction monitoring(MRM)combined with positive ion mode as the mass spectrometry conditions,a method for simultaneous and rapid determination of 4 antibacterial drugs(imipenem,meropenem,vancomycin and teicoplanin)in human serum was established.Results:The determination results showed that there were no interference peaks at the retention time of 4 antibacterial drugs and 2 internal standard substances;4 antibacterial drugs had good linear relationships within their respective concentration ranges,and their correlation coefficients(r^(2))were all greater than 0.99,and the S/N of the lowest limit of quantification were all greater than 10;the precision and accuracy test results showed that the inter-day and intra-day relative standard deviations(RSDs)of determination results of 4 antibacterial drugs were all less than 10.00%,and their relative errors(REs)were all within±10.00%;the recovery rates of determination results of 4 antibacterial drugs were all between 85.00%and 115.00%;the review of stability showed that the REs of determination results of 4 antibacterial drugs were all within±10.00%at different temperatures and storage times.Conclusion:LC-MS/MS can determine the contents of 4 antibacterial drugs(imipenem,meropenem,vancomycin and teicoplanin)in serum simultaneously and rapidly,and has high precision and accuracy and strong stability;therefore,it can provide better support for clinical therapeutic drug monitoring.

关 键 词：液相色谱串联质谱法 含量测定 亚胺培南 美罗培南 万古霉素 替考拉宁 

分 类 号：R978.1[医药卫生—药品] R97[医药卫生—药学]