10.1021/ac302308p.s001
Ingela Lanekoff
Ingela
Lanekoff
Mathew Thomas
Mathew
Thomas
James
P. Carson
James
P.
Carson
Jordan N. Smith
Jordan N.
Smith
Charles Timchalk
Charles
Timchalk
Julia Laskin
Julia
Laskin
Imaging Nicotine in Rat
Brain Tissue by Use of Nanospray
Desorption Electrospray Ionization Mass Spectrometry
American Chemical Society
2013
drug distribution impacts function
Rat Brain Tissue
detection
approach
imaging
rat brain tissue sections
vivo drug administration
image
analyte
Nanospray Desorption Electrospray Ionization Mass SpectrometryImaging mass spectrometry
Nanospray desorption electrospray ionization
tissue sections
2013-01-15 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Imaging_Nicotine_in_Rat_Brain_Tissue_by_Use_of_Nanospray_Desorption_Electrospray_Ionization_Mass_Spectrometry/2452078
Imaging mass spectrometry offers simultaneous spatially
resolved
detection of drugs, drug metabolites, and endogenous substances in
a single experiment. This is important when evaluating effects of
a drug on a complex organ system such as the brain, where there is
a need to understand how regional drug distribution impacts function.
Nanospray desorption electrospray ionization, nano-DESI, is a new
ambient technique that enables spatially resolved analysis of a variety
of samples without special sample pretreatment. This study introduces
an experimental approach for accurate spatial mapping of drugs and
metabolites in tissue sections by nano-DESI imaging. In this approach,
an isotopically labeled standard is added to the nano-DESI solvent
to compensate for matrix effects and ion suppression. The analyte
image is obtained by normalizing the analyte signal to the signal
of the standard in each pixel. We demonstrate that the presence of
internal standard enables online quantification of analyte molecules
extracted from tissue sections. Ion images are subsequently mapped
to the anatomical brain regions in the analyzed section by use of
an atlas mesh deformed to match the optical image of the section.
Atlas-based registration accounts for the physical variability between
animals, which is important for data interpretation. The new approach
was used for mapping the distribution of nicotine in rat brain tissue
sections following in vivo drug administration. We demonstrate the
utility of nano-DESI imaging for sensitive detection of the drug in
tissue sections with subfemtomole sensitivity in each pixel of a 27
μm × 150 μm area. Such sensitivity is necessary for
spatially resolved detection of low-abundance molecules in complex
matrices.