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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
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Medicinsk masspektrometri)
AstraZeneca R&D.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Medicinsk masspektrometri)
2012 (English)In: Rapid Communications in Mass Spectrometry, ISSN 0951-4198, E-ISSN 1097-0231, Vol. 26, no 5, 494-498 p.Article in journal (Refereed) Published
Abstract [en]

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 mm, 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.

Place, publisher, year, edition, pages
2012. Vol. 26, no 5, 494-498 p.
National Category
Pharmaceutical Sciences
URN: urn:nbn:se:uu:diva-166369DOI: 10.1002/rcm.6125ISI: 000299782800002OAI: oai:DiVA.org:uu-166369DiVA: diva2:476171
Available from: 2012-01-11 Created: 2012-01-11 Last updated: 2012-05-11Bibliographically approved

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Goodwin, Richard JAAndrén, Per E
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