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Wendy Zhong, Merck
Tuesday, February 16, 2021, 11:00am - 12:00pm

Wendy ZhongLabel Free Molecular Imaging by High Resolution Mass Spectrometry—It’s Application in Pharmaceutical Industry

Matrix-assisted Laser Desorption Ionization mass spectrometry imaging (MALDI-MSI) has been widely applied in direct tissue analyses to characterize the biological distribution of a wide variety of molecules including small molecule metabolites, lipids, peptides and proteins. MSI is increasingly being used throughout the pharmaceutical industry owing to its molecular specificity over conventional imaging modalities such as quantitative whole-body autoradiography and immunohistochemistry, which cannot differentiate parent drug versus metabolites. These advantages of MALDI-MSI also make it a promising analytical tool for the analysis of a wide range of drug formulation-based applications by simultaneous monitoring of formulation uniformity, chemical composition, contamination, degradation, and drug release. 

In this presentation, I will discuss several unique/innovative approaches we developed and applied to solve challenge problems during drug discovery and development.  Fatty liver disease phenotype is characterized by both an increase in the concentration and synthesis rate of neutral lipids (NL) across the liver. The spatial distribution of multiple lipids classes is poorly characterized in fatty liver disease. A novel method was development to enhance ionization of neutral lipid via Sodium-Doped Gold-Assisted Laser Desorption Ionization.  This method can allow investigators to obtain spatial resolution of lipogenic flux by coupling imaging mass spectrometry and isotope tracers.   Long-acting injectable (LAI) implants can deliver a drug over the course of several weeks to years; reducing the dosing frequency and improving patient adherence.  An innovative approach of using MALDI-MSI to characterize the drug release process from LAI implants was developed.  This method provides definitive molecular level information about the chemical composition as well as the distribution of the APIs simultaneously. This is crucial information for a better understanding of the underlying drug release mechanisms and the effect of formulation on drug distribution uniformity within the LAP and on release kinetics.


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