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

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.

Mass spectrometry imaging for drug distribution studies

“…Additional studies have shown LESA to provide semi-quantitative distribution data for drugs and their metabolites, which was in agreement with quantitative WBA [107,108].…”

Mass Spectrometry Imaging of Therapeutics from Animal Models to Three-Dimensional Cell Cultures

“…LESA has been applied to map the distribution of drugs like terfenadine 83 , moxifloxacin 84 , chloroquine and its metabolites 85 in sections from whole body, organs or tissues of rat, and the data was validated against WBA, DESI, or MALDI-MSI approaches. In other studies, LESA MSI also enabled semi-quantification of drugs and their metabolites, and the results correlated with quantitative WBA data 86–87 .…”

Qualitative and quantitative mass spectrometry imaging of drugs and metabolites

“…Front-end separation would have the biggest impact on dynamic range, and some recently developed liquid extraction ( LE ) methods have made it possible to separate compounds from tissue microsections using LC [102, 103]. Small liquid junctions can make contact with the surface of the tissue and collect local molecules to be separated by LC, effectively decoupling analyte extraction from ionization.…”