Utility of spatially-resolved atmospheric pressure surface sampling and ionization techniques as alternatives to mass spectrometric imaging (MSI) in drug metabolism

Journal Article · Sat Jan 01 00:00:00 EST 2011 · Xenobiotica

DOI:https://doi.org/10.3109/00498254.2011.587550· OSTI ID:1081882

Blatherwick, Eleanor Q. ^[1]; Van Berkel, Gary J ^[2]; Pickup, Kathryn ^[3]; Johansson, Maria K. ^[3]; Beaudoin, Marie-Eve ^[4]; Cole, Roderic ^[2]; Day, Jennifer M. ^[5]; Iverson, Suzanne ^[3]; Wilson, Ian D. ^[5]; Scrivens, James H. ^[1]; Weston, Daniel J. ^[5]

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1. University of Warwick, UK
2. ORNL
3. AstraZeneca R&D Sweden
4. AstraZeneca, USA
5. AstraZeneca R&D, UK

1. 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. 2. 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. 3. 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. 4. 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.

• Research Organization: Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
• Sponsoring Organization: Work for Others (WFO)
• DOE Contract Number: DE-AC05-00OR22725
• OSTI ID: 1081882
• Journal Information: Xenobiotica, Vol. 41, Issue 8; ISSN 0049--8254
• Country of Publication: United States
• Language: English

Related Subjects

Mass spectrometry imaging (MSI)
drug metabolism
drug disposition
liquid microjunction surface sampling probe (LMJ-SSP)
liquid extraction surface analysis (LESA)
ambient surface sampling
matrix-assisted laser desorption ionization (MALDI)