Localization and analyses of small drug molecules in rat brain tissue sections
Localization and analyses of small drug molecules in rat brain tissue sections
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DOI：
10.1021/ac050868d
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发表时间：
2005-10-15
影响因子：
7.4
通讯作者：
Woods, AS
中科院分区：
文献类型：
--
作者：
Wang, HYJ;Jackson, SN;Woods, AS
传统的检测组织中药物的方法需要组织均质，这就排除了药物的定位和定位。放射自显影的使用可以弥补这一缺点。然而，它需要昂贵的定制合成的放射性药物。近年来，基质辅助激光解吸电离质谱仪(MALDI-MS)和MALDI-MS/MS在样品制备方面的改进为药物的原位检测提供了一种新的方法。在这项工作中，大鼠脑内注射氯异丹明或腹腔注射可卡因和速冻后收集脑组织。将MALDI矩阵直接应用于14 mm厚的大脑冰冻切片并获得光谱。通过MS/MS进一步确认了药物的身份，仔细的基质选择和组织准备可以成功地检测到药物，并绘制出它们在大脑不同区域的相对丰度图。这种新方法具有简单、安全、准确、快速、成本低、样品消耗少等特点，在成像、药代动力学和毒理学方面显示出潜在的应用前景。
Traditional detection of drugs in tissue requires tissue homogenization, which precludes the mapping and localization of drugs. The use of autoradiography could compensate for such shortcoming. However, it requires expensive custom-synthesized radioactive drugs. Recent improvement in sample preparation for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and MALDI-MS/MS provides an alternative approach for in situ drug detection. In this work, rat brains were collected after intracranial injection of chlorisondamine or intraperitoneal injection of cocaine and snap frozen. MALDI matrixes were applied directly to 14-mu m brain cryosections and spectra acquired. The identity of the drugs was further confirmed by MS/MS. Careful matrix selection and tissue preparation allows for the successful detection of drugs and the mapping of their relative abundance across various regions of the brain. This new method is simple, safe, accurate, fast, cost-effective, and low in sample consumption and shows potential for imaging, pharmacokinetics, and toxicology applications.