Estimating the Human Skin Permeation of Neutral Organic Compounds Using Reversed-Phase Liquid Chromatography and...

Area of Science:

• Pharmacology and Toxicology
• Analytical Chemistry
• Dermatology

Background:

• Accurate determination of human skin permeation is crucial for topical drug development, cosmetics, and occupational safety.
• Traditional in-vitro methods like Franz cells can be time-consuming and difficult to automate.
• Surrogate chromatographic models offer a potentially faster and automatable alternative for skin permeation estimation.

Purpose of the Study:

• To evaluate alternative organic mobile modifiers for constructing surrogate chromatographic models.
• To estimate the human skin permeation of small neutral organic compounds.
• To identify optimal solvent systems for rapid and accurate skin permeation prediction.

Main Methods:

• Utilized surrogate chromatographic systems with Kinetex C18 stationary phase.
• Evaluated acetone, tetrahydrofuran, and 2-propanol as mobile modifiers.
• Compared prediction errors of developed chromatographic models against experimental data.

Main Results:

• Solvent systems of 70% (v/v) acetone and 70% (v/v) 1:1 tetrahydrofuran: 2-propanol yielded the best results.
• Achieved prediction errors of 0.180-0.231 and 0.214-0.254 log units, respectively.
• Demonstrated the efficacy of these models for estimating skin permeation.

Conclusions:

• Surrogate chromatographic models are a viable rapid screening tool for human skin permeation.
• Optimized solvent systems enable efficient estimation of permeation for small neutral organic compounds.
• This approach can accelerate drug development and safety evaluations in relevant industries.