title: Evaluation of the suitability of chromatographic systems to predict human skin permeation of neutral compounds.
abstract: Several chromatographic systems (three systems of high-performance liquid chromatography and two micellar electrokinetic chromatography systems) besides the reference octanol-water partition system are evaluated by a systematic procedure previously proposed in order to know their ability to model human skin permeation. The precision achieved when skin-water permeability coefficients are correlated against chromatographic retention factors is predicted within the framework of the solvation parameter model. It consists in estimating the contribution of error due to the biological and chromatographic data, as well as the error coming from the dissimilarity between the human skin permeation and the chromatographic systems. Both predictions and experimental tests show that all correlations are greatly affected by the considerable uncertainty of the skin permeability data and the error associated to the dissimilarity between the systems. Correlations with much better predictive abilities are achieved when the volume of the solute is used as additional variable, which illustrates the main roles of both lipophilicity and size of the solute to penetrate through the skin. In this way, the considered systems are able to give precise estimations of human skin permeability coefficients. In particular, the HPLC systems with common C18 columns provide the best performances in emulating the permeation of neutral compounds from aqueous solution through the human skin. As a result, a methodology based on easy, fast, and economical HPLC measurements in a common C18 column has been developed. After a validation based on training and test sets, the method has been applied with good results to the estimation of skin permeation of several hormones and pesticides.
authors.affiliation: Departament de Química Analítica and Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Martí i Franquès, 1-11, E-08028 Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Hidalgo-Rodríguez
authors.forename: Sara
authors.initials: S
authors.lastname: Soriano-Meseguer
authors.forename: Elisabet
authors.initials: E
authors.lastname: Fuguet
authors.forename: Clara
authors.initials: C
authors.lastname: Ràfols
authors.forename: Martí
authors.initials: M
authors.lastname: Rosés
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D002845:Chromatography / Q000379:methods; D006801:Humans; D008954:Models, Biological; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D015203:Reproducibility of Results; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000502:physiology; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D013656:Taurocholic Acid / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D014867:Water; D012967:Sodium Dodecyl Sulfate; D013656:Taurocholic Acid; D020003:1-Octanol
keywords: High-performance liquid chromatography; Micellar electrokinetic chromatography; Octanol–water partition; Quantitative structure-activity relationships; Skin permeation prediction