Direct analysis of drug candidates in tissue by matrix-assisted laser desorption/ionization mass spectrometry
Direct analysis of drug candidates in tissue by matrix-assisted laser desorption/ionization mass spectrometry
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DOI：
10.1002/jms.525
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发表时间：
2003-10-01
影响因子：
2.3
通讯作者：
Caprioli, RM
中科院分区：
文献类型：
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作者：
Reyzer, ML;Hsieh, YS;Caprioli, RM
基质辅助激光解吸/电离质谱（MALDI-MS）已用于直接分析完整组织中的药物化合物并对其进行成像。采用MALDI-QqTOFMS（QSTAR），通过监测质子化药物（m/z 695.4）解离为其主要片段（m/z 228.1），明确测定小鼠肿瘤组织中的抗肿瘤药物SCH 226374。第二种药物化合物A在口服给药后在大鼠脑组织切片中检测到，剂量范围为1-25 mg/kg。使用常规高效液相色谱/串联质谱法（HPLC/MS/MS）程序从全脑匀浆中定量化合物A，显示全脑中药物的浓度从低的24 ng/g变化到高的1790 ng/g。通过MALDI-QqTOF在每个剂量的样品中成功检测到候选药物，覆盖约两个数量级的范围。此外，在各剂量下的MALDI-QqTOFMS强度与HPLC/MS/MS结果之间观察到良好的相关性。因此，MALDI-MS响应与组织中的药物量成比例。开发定制软件以便于使用MALDI-QqTOF质谱仪对组织中的小分子进行成像。获得显示SCH 226374在肿瘤组织中的空间定位和化合物A在脑组织中的空间定位的图像。版权所有（C）2003约翰威利父子有限公司。
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been used to directly analyze and image pharmaceutical compounds in intact tissue. The anti-tumor drug SCH 226374 was unambiguously determined in mouse tumor tissue using MALDI-QqTOFMS (QSTAR) by monitoring the dissociation of the protonated drug at m/z 695.4 to its predominant fragment at m/z 228.1. A second drug, compound A, was detected in slices of rat brain tissue following oral administration with doses ranging from 1-25 mg/kg. Quantitation of compound A from whole brain homogenates using routine high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) procedures revealed that concentrations of the drug in whole brain varied from a low of 24 ng/g to a high of 1790 ng/g. The drug candidate was successfully detected by MALDI-QqTOF in samples from each dose, covering a range of approximately two orders of magnitude. In addition, good correlation was observed between the MALDI-QqTOFMS intensities at each dose with the HPLC/MS/MS results. Thus the MALDI-MS response is proportional to the amount of drug in tissue. Custom software was developed to facilitate the imaging of small molecules in tissue using the MALDI-QqTOF mass spectrometer. Images revealing the spatial localization of SCH 226374 in tumor tissue and compound A in brain tissue were acquired. Copyright (C) 2003 John Wiley Sons, Ltd.