Targeted Strategy to Analyze Antiepileptic Drugs in Human Serum by LC-MS/MS and LC-Ion Mobility-MS.

Targeted Strategy to Analyze Antiepileptic Drugs in Human Serum by LC-MS/MS and LC-Ion Mobility-MS.
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通过LC-MS/MS和LC-ION Mobility-MS分析人血清中抗癫痫药的针对性策略。

DOI:
10.1021/acs.analchem.0c03172
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发表时间:
2020-11-03
影响因子:
7.4
通讯作者:
McLean, John A.
McLean, John A.
中科院分区:
化学1区
文献类型:
--
作者:
Davis, Don E., Jr.;Sherrod, Stacy D.;Gant-Branum, Randi L.;Colby, Jennifer M.;McLean, John A.

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常规的小分子分析具有挑战性,因为需要高选择性和/或低定量限。本文报道了液相色谱-串联质谱(LC-MS/MS)定量测定人血清中14种抗癫痫药物(aed)的方法。对于本文所述的优化LC-MS/MS方法,我们应用临床和实验室标准协会(CLSI) LC-MS C62-A文件和美国食品和药物管理局(FDA)生物分析方法验证行业指南中概述的指南来评估分析的质量。在这些研究中,对AED的线性、分析物回收率、基质效应、精密度和准确度进行了评估。采用液相色谱-漂移管离子迁移质谱法(LC-DTIM-MS),通过精确的质量和碰撞截面(CCS)测量,提高了AED鉴定的可信度。LC-DTIM-MS方法还用于评估漂移管CCS测量在分离和鉴定AED结构异构体和其他AED中的能力。这些数据表明,信息的另一个维度,即CCS测量,提供了AED分析所需的结构信息的正交维度。使用LC-MS/MS和LC-DTIM-MS进行多路AED测量,由于在这些类型的分析研究中具有高精度的能力,因此有可能更好地优化给药。综上所述,这些数据还表明,使用这些分析技术可以提高对小分子鉴定和定量的信心。
Routine small-molecule analysis is challenging owing to the need for high selectivity and/or low limits of quantification. This work reports a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify 14 antiepileptic drugs (AEDs) in human serum. For the optimized LC-MS/MS method described herein, we applied the guidelines outlined in the Clinical and Laboratory Standards Institute (CLSI) LC-MS C62-A document and the U.S. Food and Drug Administration (FDA) Bioanalytical Method Validation Guidance for Industry to evaluate the quality of the assay. In these studies, AED linearity, analyte recovery, matrix effects, precision, and accuracy were assessed. Using liquid chromatography-drift tube ion mobility-mass spectrometry (LC-DTIM-MS), a qualitative method was also used to increase confidence in AED identification using accurate mass and collision cross section (CCS) measurements. The LC-DTIM-MS method was also used to assess the ability of drift tube CCS measurements to aid in the separation and identification of AED structural isomers and other AEDs. These data show that another dimension of information, namely CCS measurements, provides an orthogonal dimension of structural information needed for AED analysis. Multiplexed AED measurements using LC-MS/MS and LC-DTIM-MS have the potential to enable better optimization of dosing owing to the high precision capabilities available in these types of analytical studies. Taken together, these data also show the ability to increase confidence in small-molecule identification and quantification using these analytical technologies.
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