MALDI imaging facilitates new topical drug development process by determining quantitative skin distribution profiles.

D. Bonnel (1), R. Legouffe (1), AH. Eriksson (2), RW. Mortensen (2), F. Pamelard (1), J. Stauber (1, 3), KT. Nielsen (4).

1 ImaBiotech SAS, Parc Eurasanté, 885 Avenue Eugène Avinée, 59120, Loos, France.
2 LEO Pharma A/S, Industriparken 55, 2750, Ballerup, Denmark.
3 ImaBiotech Corp, 44 Manning Road Unit 3, Billerica, MA, 01821, USA.
LEO Pharma A/S, Industriparken 55, 2750, Ballerup, Denmark.

Analytical and Bioanalytical Chemistry, April 2018, Volume 410, Issue 11

Generation of skin distribution profiles and reliable determination of drug molecule concentration in the target region are crucial during the development process of topical products for treatment of skin diseases like psoriasis and atopic dermatitis. Imaging techniques like mass spectrometric imaging (MSI) offer sufficient spatial resolution to generate meaningful distribution profiles of a drug molecule across a skin section. In this study, we use matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to generate quantitative skin distribution profiles based on tissue extinction coefficient (TEC) determinations of four different molecules in cross sections of human skin explants after topical administration. The four drug molecules: roflumilast, tofacitinib, ruxolitinib, and LEO 29102 have different physicochemical properties. In addition, tofacitinib was administrated in two different formulations. The study reveals that with MALDI-MSI, we were able to observe differences in penetration profiles for both the four drug molecules and the two formulations and thereby demonstrate its applicability as a screening tool when developing a topical drug product. Furthermore, the study reveals that the sensitivity of the MALDI-MSI techniques appears to be inversely correlated to the drug molecules’ ability to bind to the surrounding tissues, which can be estimated by their Log D values. Graphical abstract.

Keywords: Drug distribution; Human skin; MALDI-MSI; Mass spectrometry imaging; Quantification; Skin penetration

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