Mass spectrometry imaging unveils the fate of azithromycin in zebrafish: Uptake, distribution, transformation, and metabolic impact

Most of the published articles have reported antibiotics as emerging pollutants. Upon entering organisms, they rapidly accumulate in the sites of action, with varying tissue distributions and the potential to interfere normal metabolism of endogenous metabolites. However, the simultaneous clarification of the spatial distribution of exogenous and endogenous metabolites has seldom been achieved. Mass spectrometry imaging (MSI) allows the label-free detection of endogenous and exogeneous molecules within tissues. Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was used in this study to explore the bioaccumulation, elimination and transformation process of azithromycin (AZM) over blue-striped zebrafish. AZM in zebrafish showed a first-order kinetic model, and the intestine was identified to be areas with the longest t_1/2 (3.5 days). The zebrafish showed a striking ability for biotransformation as three biotransformation products (BTPs) of AZM have been detected mostly in the zebrafish. The spatial distributions of endogenous molecules were further examined to observe more differences in intensity and types, a significant impact on the Glycerol phospholipids (GP), amino acids (AA), Ceramide (Cer), glycerolipids (GL) and Sphingomyelin (SM) was found. These results indicate that MSI contributes to the research on drug distribution and metabolism, helps deepen the understanding of drug metabolism, accurately locate the action targets, and improve the efficiency and quality of drug development.