Quantitative MALDI-MSn Analysis of Cocaine in the Autopsied Brain of a Human Cocaine User Employing a Wide Isolation Window and Internal Standards
Quantitative MALDI-MSn Analysis of Cocaine in the Autopsied Brain of a Human Cocaine User Employing a Wide Isolation Window and Internal Standards
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DOI：
10.1016/j.jasms.2009.12.014
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发表时间：
2010-04-01
影响因子：
3.2
通讯作者：
Yost, Richard A.
中科院分区：
文献类型：
--
作者：
Reich, Richard F.;Cudzilo, Kasia;Yost, Richard A.
组织中药物的检测通常需要大量的样品制备，其中首先将组织均质化，然后进行药物提取，然后通过LC/MS最终分析提取物。直接分析完整组织中的药物将消除样品预处理引入的任何并发症。基质辅助激光解吸/电离串联质谱法（MALDI-MS）用于定量慢性可卡因使用者死后脑组织中的可卡因。结果表明，串联质谱（MS 2和MS 3）增加了选择性，这对于区分分析物离子与背景离子（如基质簇和脑组织中发现的内源性化合物）至关重要。它还表明，使用内标校正定量MALDI过程中的信号变异性，这可能是由不均匀的晶体形成，不一致的样品制备，和激光拍摄到拍摄的变异性。所开发的MALDI-MS”方法允许使用宽隔离窗口来隔离分析物和内标靶离子的单个MS 3实验。与使用分别分离目标分析物和内标离子的两个交替MS 3实验相比，该方法显示出定量分析的精密度提高[相对标准偏差百分比（%RSD）降低10-20倍]。（J Am Soc Mass Spectrom 2010，21，564-571）（C）2010年美国质谱学会
Detection of drugs in tissue typically requires extensive sample preparation in which the tissue is first homogenized, followed by drug extraction, before the extracts are finally analyzed by LC/MS. Directly analyzing drugs in intact tissue would eliminate any complications introduced by sample pretreatment. A matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS") method as been developed for the quantification of cocaine present in postmortem brain tissue of a chronic human cocaine user. It is shown that tandem mass spectrometry (MS2 and MS3 increase selectivity, which is critical for differentiating analyte ions from background ions such as matrix clusters and endogenous compounds found in brain tissue. It is also shown that the use of internal standards corrects for signal variability during quantitative MALDI, which can be caused by inhomogeneous crystal formation, inconsistent sample preparation, and laser shot-to-shot variability. The MALDI-MS" method developed allows for a single MS3 experiment that uses a wide isolation window to isolate both analyte and internal standard target ions. This method is shown to provide improved precision [similar to 10-20 times reduction in percent relative standard deviation (%RSD)] for quantitative analysis compared to using two alternating MS3 experiments that separately isolate the target analyte and internal standard ions. (J Am Soc Mass Spectrom 2010, 21, 564-571) (C) 2010 American Society for Mass Spectrometry