Department of Chemistry, University of Florida, Gainesville, Florida 32611-7200, USA.
J Am Soc Mass Spectrom. 2010 Apr;21(4):564-71. doi: 10.1016/j.jasms.2009.12.014. Epub 2010 Jan 4.
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(n)) 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 (MS(2) and MS(3) 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(n) method developed allows for a single MS(3) experiment that uses a wide isolation window to isolate both analyte and internal standard target ions. This method is shown to provide improved precision [approximately 10-20 times reduction in percent relative standard deviation (%RSD)] for quantitative analysis compared to using two alternating MS(3) experiments that separately isolate the target analyte and internal standard ions.
检测组织中的药物通常需要进行广泛的样品制备，首先要将组织均质化，然后进行药物提取，最后通过 LC/MS 对提取物进行分析。直接分析完整组织中的药物可以消除样品预处理带来的任何复杂问题。本文建立了一种基质辅助激光解吸/电离串联质谱（MALDI-MS(n)）方法，用于定量分析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)）可以提高选择性，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。还表明，使用内标可以校正定量 MALDI 过程中的信号变化，这种变化可能是由晶体形成不均匀、样品制备不一致和激光射击变化引起的。开发的 MALDI-MS(n)方法允许进行单次 MS(3)实验，该实验使用宽隔离窗口来分离分析物和内标靶离子。与使用两种交替的 MS(3)实验（分别分离目标分析物和内标离子）相比，该方法在定量分析中可提供更高的精度（大约减少 10-20%的相对标准偏差（%RSD））。
