Abstract Teeth and jawbone are mineralized tissues with a strong capacity to incorporate and retain small exogenous molecules, e.g., pharmaceuticals. Their limited metabolic turnover provides a stable record of exposure for a long time after administration. These features make them well-suited for spatially resolved chemical analysis. This study presents the first proof-of-concept application of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to visualize both endogenous metabolites and clinically relevant pharmaceuticals in situ within human dental hard tissues and jawbone. Human teeth, jawbone, and teeth with adjacent jawbone from four patients were sectioned and analyzed using high-resolution Orbitrap MSI, followed by metabolite annotation in METASPACE and confirmatory analysis. MSI successfully mapped endogenous metabolites such as arginine, phosphatidylcholine, and lysophosphatidylcholine, and revealed distinct distribution patterns of the pharmaceuticals lidocaine, bupivacaine, and chlorhexidine. Injected analgesics were predominantly localized within the tissues, whereas topically applied chlorhexidine was confined to the surface. The study demonstrates that MSI can detect retained pharmaceuticals in mineralized tissues and differentiate their spatial patterns according to route of administration. The findings highlight the value of MSI as a complement to conventional LC-MS by providing spatial context that cannot be obtained from homogenized samples. MSI can reveal the spatial distribution and accumulation of both endogenous metabolites and exogenous drugs within dental hard tissues and jawbone. Such spatial insight is valuable for understanding how pharmaceuticals interact with mineralized tissues, where they may accumulate or undergo biotransformation, and may ultimately support the development and optimization of therapeutics for dental infections such as osteomyelitis and periodontitis. Graphical abstract
Amin et al. (Thu,) studied this question.