Blatherwick, Eleanor Q., Van Berkel, Gary J., Pickup, Kathryn, Johansson, Maria K., Beaudoin, Marie-Eve, Cole, Roderic O., Day, Jennifer M., Iverson, Suzanne, Wilson, Ian D., Scrivens, James H. and Weston, Daniel J.. (2011) Utility of spatially-resolved atmospheric pressure surface sampling and ionization techniques as alternatives to mass spectrometric imaging (MSI) in drug metabolism. Xenobiotica, Vol.41 (No.8). pp. 720-734. ISSN 0049-8254

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Abstract

Tissue distribution studies of drug molecules play an essential role in the pharmaceutical industry and are commonly undertaken using quantitative whole body autoradiography (QWBA) methods.

The growing need for complementary methods to address some scientific gaps around radiography methods has led to increased use of mass spectrometric imaging (MSI) technology over the last 5 to 10 years. More recently, the development of novel mass spectrometric techniques for ambient surface sampling has redefined what can be regarded as ""fit-for-purpose"" for MSI in a drug metabolism and disposition arena.

Together with a review of these novel alternatives, this paper details the use of two liquid microjunction (LMJ)-based mass spectrometric surface sampling technologies. These approaches are used to provide qualitative determination of parent drug in rat liver tissue slices using liquid extraction surface analysis (LESA) and to assess the performance of a LMJ surface sampling probe (LMJ-SSP) interface for quantitative assessment of parent drug in brain, liver and muscle tissue slices.

An assessment of the utility of these spatially-resolved sampling methods is given, showing interdependence between mass spectrometric and QWBA methods, in particular there emerges a reason to question typical MSI workflows for drug metabolism; suggesting the expedient use of profile or region analysis may be more appropriate, rather than generating time-intensive molecular images of the entire tissue section.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology R Medicine > RM Therapeutics. Pharmacology
Divisions:	Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Drugs -- Metabolism, Mass spectrometry, Autoradiography, Whole body imaging
Journal or Publication Title:	Xenobiotica
Publisher:	Informa Healthcare
ISSN:	0049-8254
Official Date:	August 2011
Dates:	Date Event August 2011 Published
Volume:	Vol.41
Number:	No.8
Page Range:	pp. 720-734
Identification Number:	10.3109/00498254.2011.587550
Status:	Peer Reviewed
Publication Status:	Published
Funder:	Oak Ridge National Laboratory (ORNL) , AstraZeneca (Firm), United States. Dept. of Energy (DOE) , Medical Research Council (Great Britain) (MRC)
Grant number:	DE-AC05-00OR22725 (DOE)
URI:	http://wrap.warwick.ac.uk/id/eprint/38765

Data sourced from Thomson Reuters' Web of Knowledge

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