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The significance of ambient-temperature on pharmaceutical and endogenous compound abundance and distribution in tissues sections when analyzed by matrix-assisted laser desorption/ionization mass spectrometry imaging

Authors


R. J. A. Goodwin, Global Distribution Imaging, DMPK IM, AstraZeneca R&D, Södertälje, Sweden.

E-mail: richard.goodwin@astrazeneca.com

Abstract

RATIONALE

Mass spectrometry imaging has proven to be a complementary assay to the traditional labeled-compound studies employed in drug research and development. However, there has been limited examination of the technical limitations of the technique with respect to small molecule stability in samples.

METHODS

Raclopride dosed rat brain tissue sections (single dose i.v. 2 mg/kg) were allowed to warm to room temperature for 0 to 5 min prior to either a solvent-based wet matrix-assisted laser desorption/ionization (MALDI) matrix or a solvent-free dry MALDI matrix being applied. Subsequent MS imaging analysis was at a spatial resolution of 200 µm, performed using a MALDI TOF/TOF (Ultraflex II, Bruker Daltonics).

RESULTS

MALDI-MS has been used to monitor the time-dependent appearance and loss of small molecule abundance in tissue sections brought rapidly to room temperature for short periods of time. The abundances of a range of markers were seen to vary across the time course, both increasing and decreasing. The intensity of some markers changed significantly within 1 min. Importantly, the abundance of raclopride was seen to decrease over the 5-min time period examined.

CONCLUSIONS

The results strongly indicate that considerable care is required to allow comparison of both pharmaceutical and endogenous compounds between MALDI-MSI experiments and also has implications for the standard practice of thaw-mounting multiple tissue sections onto MALDI-MS targets during MSI experiments. Copyright © 2012 John Wiley & Sons, Ltd.

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