Localization and analyses of small drug molecules in rat brain tissue sections.
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.
Wang
Hay-Yan J
HY
Cellular Neurobiology Branch, NIDA-IRP, NIH, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA.
Jackson
Shelley N
SN
McEuen
Jonathan
J
Woods
Amina S
AS
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002714:Chlorisondamine / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D003042:Cocaine / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D013058:Mass Spectrometry; D015394:Molecular Structure; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D014018:Tissue Distribution
D003042:Cocaine; D002714:Chlorisondamine