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超高压液相色谱-串联质谱法测定患儿血清中阿米卡星的浓度
林志燕,黄晓会,杨萍,陆晓彤
0
(上海交通大学医学院附属新华医院,上海 200092)
摘要:
目的:建立超高压液相色谱-串联质谱(UHPLC-MS/MS)法测定儿童血清中阿米卡星药物浓度的分析方法,并将该方法应用于临床样本的检测,指导临床合理用药。方法:血清样品经甲醇蛋白沉淀,以异帕米星为内标,采用Agilent Poroshell120 HILIC-Z(2.1 mm×100 mm,2.7 μm)色谱柱分离,流动相A:100 mM醋酸铵溶液(含1%甲酸),流动相B:乙腈(含1%甲酸),梯度洗脱。电喷雾离子源,多反应离子监测模式,采用正离子模式进行检测,检测离子通道为m/z 586.2/163.1(阿米卡星)和m/z 570.2/411.4(内标)。结果:阿米卡星在0.625~40.000 μg/mL范围内线性关系良好(r=0.999 6),日内和日间精密度<11.14%,准确度为91.76%~110.31%,基质效应95.02%~103.23%,提取回收率90.24%~96.29%。结论:本方法简单、快速、灵敏、准确,适用于人血清阿米卡星浓度分析测定。将该方法用于临床6例儿科患儿阿米卡星药物浓度监测,测定结果显示患儿的稳态谷浓度和峰浓度个体差异较大,提示阿米卡星在治疗过程中应进行药物浓度监测。
关键词:  阿米卡星  超高压液相色谱-串联质谱  治疗药物浓度监测
DOI:doi:10.13407/j.cnki.jpp.1672.108X.2019.12.009
基金项目:
Ultra High Pressure Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Amikacin in Children Serum
Lin Zhiyan, Huang Xiaohui, Yang Ping, Lu Xiaotong
(Xinhua Hospital Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China)
Abstract:
Objective: To develop a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for determination of amikacin in human plasma. The method was applied to clinical samples, especially for children. Methods: Samples were extracted with methanol, Isepamicin was used as internal standard (IS). The analysis was carried out on the Agilent Poroshell120 HILIC-Z (2.1×100 m, .7μm) column with gradient elution. The mobile phase was 100 mM ammonium acetate (containing 1% formic acid) and acetonitrile (containing 1% formic acid). The determination was performed on a triple quadrupole tandem mass spectrometer by multiple reactions monitoring (MRM) mode via electrospray ionization (ESI) source. The detection was performed in selected reaction monitoring mode at ion transition of m/z 586.2/163.1 for amikacin and m/z 570.2/411.4 for IS. Results: The standard curves were linear (r=0.999 6) over the concentration range of 0.625-40.000 μg/mL. The intra-day and inter-day precision was less than 11.14%; The accuracy ranged from 91.76% to 110.31%;The matrix effect ranged from 95.02% to 103.23%; The values of extraction recovery was from 90.23% to 96.29%. Conclusion: The determination method of amikacin was simple, rapid, sensitive and accurate, and was suitable for the TDM of amikacin. The method was applied to monitor the concentration of amikacin in 6 pediatric patients. The results showed that there were great individual differences in the concentration of amikacin. It was suggested that concentration of amikacin should be monitored during treatment.
Key words:  amikacin  UHPLC-MS/MS  therapeutic drug monitoring

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