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引用本文:赵婷慧,贡雪芃,向东,刘璐,李宁红,余恒毅,李喜平,杜光.LC-MS/MS测定人血浆中多黏菌素B浓度及其应用[J].中国现代应用药学,2022,39(23):3117-3122.
ZHAO Tinghui,GONG Xuepeng,XIANG Dong,LIU Lu,LI Ninghong,YU Hengyi,LI Xiping,DU Guang.Concentration Determination of Polymyxin B in Plasma by LC-MS/MS and Its Application[J].Chin J Mod Appl Pharm(中国现代应用药学),2022,39(23):3117-3122.
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LC-MS/MS测定人血浆中多黏菌素B浓度及其应用
赵婷慧, 贡雪芃, 向东, 刘璐, 李宁红, 余恒毅, 李喜平, 杜光
华中科技大学同济医学院附属同济医院药学部, 武汉 430030
摘要:
目的 建立测定人血浆中多黏菌素B总浓度的液相色谱串联质谱(LC-MS/MS)方法,并应用于临床多黏菌素B的治疗药物监测。方法 采用Welch Ultimate LP-C18(100mm×2.1mm,5μm)色谱柱对多黏菌素B的主要成分进行色谱分离,建立时间程序为4.0min的LC-MS/MS法,以乙腈为沉淀剂进行蛋白沉淀的样品前处理,用正离子扫描以及多反应监测模式进行分析物测定。结果 多黏菌素B的总浓度线性范围为100~10000ng·mL-1,各主要成分线性系数均>0.996,批内和批间精密度RSD均≤6%,准确度为91.88%~114.02%,测定3例使用多黏菌素B患者的体内暴露量,AUC0-24h分别为39.73,64.15,107.75mg·L-1·h-1结论 本研究建立了一种稳健的测定人血浆中多黏菌素B总浓度的LC-MS/MS方法,灵敏度和特异性好,并成功用于临床上多黏菌素B的治疗药物监测。
关键词:  液相色谱串联质谱法  多黏菌素B  治疗药物监测
DOI:10.13748/j.cnki.issn1007-7693.2022.23.010
分类号:R917.101
基金项目:
Concentration Determination of Polymyxin B in Plasma by LC-MS/MS and Its Application
ZHAO Tinghui, GONG Xuepeng, XIANG Dong, LIU Lu, LI Ninghong, YU Hengyi, LI Xiping, DU Guang
Department of Pharmacy, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Abstract:
OBJECTIVE To establish a liquid chromatography tandem mass spectrometry(LC-MS/MS) method for the determination of polymyxin B concentration in human plasma, and to use it for clinical drug monitoring of polymyxin B. METHODS The Welch Ultimate LP-C18(100 mm×2.1 mm, 5 μm) column was used to separate the main components of polymyxin B, and an LC-MS/MS with a time program of 4.0 min was established. Acetonitrile was used as precipitator for sample pretreatment of protein precipitation, positive ion scanning and multi-reaction detection mode were used for analyte determination. RESULTS The linear range of total polymyxin B concentration was 100-10 000 ng·mL-1. The linear coefficients of the main components were both> 0.996. The intra-assay and inter-assay precisions were both ≤ 6%, and the accuracy was 91.88%-114.02%. The in vivo exposure of three patients using polymyxin B, AUC0-24 h was 39.73, 64.15 and 107.75 mg·L-1·h-1, respectively. CONCLUSION This study has established a robust LC-MS/MS method for the determination of the total concentration of polymyxin B in human plasma, with good sensitivity and specificity, and has been successfully used for clinical monitoring the concentration of polymyxin B.
Key words:  LC-MS/MS  polymyxin B  therapeutic drug monitoring
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