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Whole‐body tissue distribution study of drugs in neonate mice using desorption electrospray ionization mass spectrometry imaging
Author(s) -
Liu Jingzhou,
Gingras Jacinthe,
Ganley Kenneth P.,
Vismeh Ramin,
Teffera Yohannes,
Zhao Zhiyang
Publication year - 2013
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.6775
Subject(s) - chemistry , mass spectrometry imaging , desorption electrospray ionization , muscle tissue , metabolite , tissue distribution , ventricle , pathology , pharmacology , chromatography , mass spectrometry , anatomy , biochemistry , medicine , chemical ionization , ion , organic chemistry , ionization
RATIONALE Although Desorption Electrospray Ionization (DESI) Mass Spectrometry Imaging (MSI) is uniquely suited for whole‐body (WB) tissue distribution study of drugs, success in this area has been difficult. Here, we present WB tissue distribution studies using DESI‐MSI and a new histological tissue‐friendly solvent system. METHODS Neonate pups were dosed subcutaneously (SC) with clozapine, compound 1 , compound 2 , or compound 3 . Following euthanization by hypothermia, neonates underwent a transcardiac perfusion (saline) to remove blood. After cryosectioning, DESI‐MSI was conducted for the WB tissue slides, followed sequentially by histological staining. RESULTS Whole‐body tissue imaging showed that clozapine and its N ‐oxide metabolite were distributed in significant amounts in the brain, spinal cord, liver, heart (ventricle), and lungs. Compound 1 was distributed mainly in the liver and muscle, and its mono‐oxygenated metabolite was detected by DESI‐MSI exclusively in the liver. Compound 2 was distributed mainly in the muscle and fatty tissue. Compound 3 was distributed mainly in fatty tissue and its metabolites were also mainly detected in the same tissue. CONCLUSIONS The results demonstrate the successful application of DESI‐MSI in whole‐body tissue distribution studies of drugs and metabolites in combination with sequential histology staining for anatomy. The results also identified lipophilicity as the driving force in the tissue distribution of the three Amgen compounds. Copyright © 2013 John Wiley & Sons, Ltd.