Visualizing Dermal Permeation of Sodium Channel Modulators by Mass Spectrometric Imaging

ABSTRACT: Determining permeability of a given compound through human skin is a principal challenge owing to the highly complex nature of dermal tissue. We describe the application of an ambient mass spectrometry imaging method for visualizing skin penetration of sodium channel modulators, including novel synthetic analogs of natural neurotoxic alkaloids, topically applied ex vivo to human skin. Our simple and label-free approach enables successful mapping of the transverse and lateral diffusion of small molecules having different physicochemical properties without the need for extensive sample preparation. Transdermal delivery of therapeutic agents represents an attractive alternative to oral or parenteral delivery and has witnessed increased clinical application in the past two decades.1 Transdermal delivery has many advantages i