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Tissue Imaging by Mass Spectrometry: A Practical Guide for the Medicinal Chemist.

Understanding the tissue distribution of therapeutic molecules is often critical for assessing their efficacy and toxicity. Unfortunately, standard methods for monitoring localized drug distribution are resource-intensive and are typically performed late in the discovery process. As a result, early development efforts often progress without detailed information on the effect that changes in structure and/or formulation have on drug localization. Recent innovations in mass spectrometry (MS) provide new options for mapping the spatial distribution of drug in tissue and allow parallel detection of endogenous species. These advances are improving access to drug distribution data early in discovery and provide insight into local biochemical changes that are directly related to drug activity. The literature on these topics is voluminous, and the technology is advancing rapidly, offering a bewildering array of options for researchers who are new to the field. To guide medicinal chemists who wish to apply these methods in their research, this technology perspective provides our views on practical applications that are currently enabled by various MS imaging (MSI) approaches, along with recommendations for how best to implement these methods in pharmaceutical R&D.