DESI-MS imaging to visualize spatial distribution of xenobiotics and endogenous lipids in the skin.

The cutaneous biodistribution method (CBM) yields a high-resolution quantitative profile of drug deposition as a function of skin depth. However, it provides limited details about drug spatial distribution or penetration pathways. Mass spectrometry imaging (MSI) can complement the detailed quantitative data generated by CBM studies. The objectives of this work were to use desorption electrospray ionization (DESI)-MSI to (i) investigate the spatial cutaneous distributions of a topically applied drug and excipient and relate them to skin structures and (ii) image endogenous skin components and combine these results to gain insight into drug penetration routes. Porcine skin was used to compare two bioequivalent creams of econazole nitrate (ECZ) and a micelle formulation based on D-α-tocopheryl succinate polyethylene glycol 1000 (TPGS). DESI-MSI successfully imaged the cutaneous spatial distribution of ECZ and TPGS in 40 µm-thick horizontal sections and vertical cross-sections of the skin. Interestingly, clinically bioequivalent formulations did not appear to exhibit the same molecular distribution of ECZ in XY-horizontal sections. DESI-MSI also enabled visualization of TPGS (m/z 772.4706), mainly in the upper epidermis (≤80 µm). In conclusion, through co-localization of drugs and excipients with endogenous elements of the skin, DESI-MSI could further our understanding of the cutaneous penetration pathways of xenobiotics.