Localization and analyses of small drug molecules in rat brain tissue sections

Abstract

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-mum 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.