Estimating the Human Skin Permeation of Neutral Organic Compounds Using Reversed‐Phase Liquid Chromatography and Alternative Organic Solvent Modifiers

Determination of human skin permeation is necessary in drug development for topical treatments, the cosmetics sector, and occupational hazard evaluation applications. When compared to the in-vitro assay experiments based on Franz cells for the determination of human skin permeation, the estimation methods based on surrogate chromatographic models are less time-consuming and can be easily automated. In this work, we evaluated surrogate chromatographic alternative organic mobile modifiers, acetone, tetrahydrofuran, and 2-propanol, for the estimation of human skin permeation of small neutral organic compounds using surrogate chromatographic systems. Solvent systems comprising 70% (v/v) acetone and 70% (v/v) 1:1 tetrahydrofuran: 2-propanol on a Kinetex C18 stationary phase demonstrated the best results for the construction of surrogate chromatographic models with prediction errors of 0.180-0.231 and 0.214-0.254 log units, respectively. Proposed surrogate chromatographic models could be used as a rapid screening tool to estimate human skin permeation of small neutral organic compounds.