A Parallel-Column LC-MS/MS Method for High-Throughput Analysis of Eight Antiepileptic Drugs in Clinical Therapeutic Drug Monitoring

A Parallel-Column LC-MS/MS Method for High-Throughput Analysis of Eight Antiepileptic Drugs in Clinical Therapeutic Drug Monitoring
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临床治疗药物监测中八种抗癫痫药物高通量分析的平行柱 LC-MS/MS 方法

DOI:
10.1007/s10337-016-3196-8
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发表时间:
2017
期刊:
影响因子:
1.7
通讯作者:
Gu Jingkai
Gu Jingkai
中科院分区:
化学4区
文献类型:
--
作者:
Yin Lei;Shi Meiyun;Wang Tingting;Zhang Miaomin;Zhao Xiaojun;Zhang Ying;Gu Jingkai

文献摘要

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摘要治疗性药物监测(TDM),即多次测量药物血浆浓度的方法,在抗癫痫药物等治疗窗口较窄的药物的临床管理中是必要的。本研究描述了一种用于人血浆中aed定量高通量分析的平行双柱LC-MS /MS系统。它将两个高效液相色谱(HPLC)系统多路复用到一个质谱仪中,与通用的单柱LC-MS /MS系统相比,提供了两倍的吞吐量增加。特异性、基质效应、回收率、线性度、精密度、准确度验证结果令人满意。8种aed的日内精密度和日间精密度均小于7.62%,准确度在- 5.06 ~ 14.00%之间。该方法用于定期监测来自1773例患者的8个aed的血浆水平。平行HPLC-MS /MS方法已被证明能够处理大量分析样品。该系统的样品通量增加了两倍,工作流程更加协调,可以轻松满足临床TDM的高通量挑战。图形抽象
AbstractTherapeutic drug monitoring (TDM), the practice of measuring drug plasma concentrations at multiple times, is necessary in the clinical management of drugs with narrow therapeutic windows, such as antiepileptic drugs (AEDs). This study describes a parallel two-column LC–MS/MS system for quantitative high-throughput analysis of AEDs in human plasma. It multiplexes two high-performance liquid chromatography (HPLC) systems into a single mass spectrometer, providing a twofold throughput increase compared to a generic single-column LC–MS/MS system. The validation results of specificity, matrix effects, recovery, linearity, precision, and accuracy were satisfactory. The intra-day precision and inter-day precision for the analysis of the eight AEDs were less than 7.62%, with the accuracy ranging between −5.06 and 14.00%. The method was used to monitor plasma levels of eight AEDs from 1773 patients on a regular basis. The parallel HPLC–MS/MS method has been demonstrated to be capable of processing large analytical samples. With a twofold increase in sample throughput and a better-coordinated workflow, the system can easily meet the high-throughput challenge in clinical TDM.Graphical Abstract