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

Abstract

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.

Keywords::

• 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)
• quantitative whole body autoradiography (QWBA)

Acknowledgements

The authors would like to thank Michael Grondine, Denise Hughes, Shaobu Weng, and Heather Blanchette (AstraZeneca Pharmaceuticals, Waltham, MA, USA); Bernard Lanoue, William Potts, Norman LeDonne, Deborah Buhrman, and Anna Zacco (AstraZeneca Pharmaceuticals, Wilmington, DE, USA); Taher Riahi (AstraZeneca R&D Södertälje); Susan Slade (University of Warwick, UK); Mark Baumert and Mark Allen (Advion Biosciences Ltd., Norwich, UK) for their valuable assistance in these works. D. J. Weston wishes to thank Prof. R. Graham Cooks (Purdue University, IN, USA) and Prof. Ron. M. A. Heeren (FOM-AMOLF, Netherlands) for use of DESI and SIMS images, respectively, as used in the composite illustration for Figure 1.

Declarations of interest

G. J. Van Berkel acknowledges support for this work at Oak Ridge National Laboratory (ORNL) from a Work for Others (WFO) agreement with AstraZeneca Pharmaceuticals, Waltham, MA, USA. ORNL is managed by UT-Battelle for the United States Department of Energy under contract number DE-AC05-00OR22725. E. Q. Blatherwick and J. H. Scrivens acknowledge research funding from the Medical Research Council (MRC), UK, under an industrial CASE studentship award, part-funded by AstraZeneca R&D Charnwood, Loughborough, UK.