MALDI-TOF Mass Spectrometry Imaging for Spatially Resolved Degradation Profiling of Solid Formulations

Abstract

Understanding the stability of the active pharmaceutical ingredient (API) and drug−excipient interactions is critical for ensuring the efficacy and shelf life of pharmaceutical formulations. This study applies matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to investigate two-dimensional (2D) and three-dimensional (3D) spatial profiling of degradants in Losartan potassium tablets that are subjected to temperature- and humidity-induced stress conditions. This approach allows for in situ visualization of API degradation and excipient compatibility within solid dosage forms. Upon stress, Losartan tablets formed dimeric and trimeric species as major degradation products. Spatial mapping revealed a gradual growth of these degradants from the control (T0) through four weeks of stress. Ion images showed distinct heterogeneity in the formation of dimer and trimer species across the tablet depth and plane; however, no preferential pattern was observed at the tablet periphery. The random distribution of degradants suggests that alongside humidity, localized microenvironments drive the degradation process. MALDI-MSI demonstrates strong potential as a high-throughput and sensitive alternative to traditional liquid chromatography-based procedures for early-stage formulation screening. Furthermore, this work suggests that when integrated with orthogonal techniques to coregister excipient domains, MALDI-MSI can serve as an emerging tool to uniquely characterize drug−excipient interactions during early-stage drug development. This provides spatially resolved insight that enhances accelerated stability assessment programs and streamline the selection of compatible excipients.