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. 2008 Jul 15;80(14):5648-53.
doi: 10.1021/ac800617s. Epub 2008 Jun 20.

MALDI-FTICR imaging mass spectrometry of drugs and metabolites in tissue

Dale S Cornett  1 , Sara L Frappier, Richard M Caprioli
Affiliations

MALDI-FTICR imaging mass spectrometry of drugs and metabolites in tissue

Dale S Cornett et al. Anal Chem. .

Abstract

A new approach is described for imaging mass spectrometry analysis of drugs and metabolites in tissue using matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance (MALDI-FTICR). The technique utilizes the high resolving power to produce images from thousands of ions measured during a single mass spectrometry (MS)-mode experiment. Accurate mass measurement provides molecular specificity for the ion images on the basis of elemental composition. Final structural confirmation of the targeted compound is made from accurate mass fragment ions generated in an external quadrupole-collision cell. The ability to image many small molecules in a single measurement with high specificity is a significant improvement over existing MS/MS based technologies. Example images are shown for olanzapine in kidney and liver and imatinib in glioma.

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Figures

Figure 1
Figure 1
FTICR images from a liver of a rat dosed with 8 mg/kg olanzapine (2 h postdose). (A) Average of all spectra collected from matrix spots on the tissue (inset image). The m/z region of the average spectrum in the regions of protonated molecule of (B) olanzapine, (C) desmethyl metabolite, and (D) hydroxymethyl metabolite. Ion images of each marked peak is inset to each spectrum.
Figure 2
Figure 2
FTICR images from the kidney of a rat dosed with 8 mg/kg olanzapine (2 h postdose). (A) Average of all spectra collected from matrix spots on the tissue (inset image). The m/z region of the average spectrum in the regions of protonated molecule of olanzapine (B), metabolite (C), and hydroxymethyl metabolite (D). Ion images of each marked peak is inset to each spectrum.
Figure 3
Figure 3
CID spectra of the proposed olanzapine (A), desmethyl metabolite (B), and hydroxymethyl metabolite (C) ions. The fragment ions observed correspond to known transitions of the respective structures.
Figure 4
Figure 4
FTICR images of imatinib and des-methyl metabolite from glioma/mouse brain (cresyl violet stained). Top spectrum: average of all spectra with expanded view of protonated molecule region (inset). Bottom spectrum: CID fragments from the nominal proposed imatinib ion.
Figure 5
Figure 5
FTICR images of hydroxymethyl OLZ and three isobaric ions.
See this image and copyright information in PMC

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