Revisiting thin-layer chromatography as a lipophilicity determination tool—A comparative study on several techniques with a model solute set

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 53; no. 4; pp. 911 - 918
• Main Authors: Komsta, Łukasz, Skibiński, Robert, Berecka, Anna, Gumieniczek, Anna, Radkiewicz, Beata, Radoń, Małgorzata
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.12.2010; Elsevier
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Chromatography, Thin Layer - methods; Fundamental and applied biological sciences. Psychology; General pharmacology; Least-Squares Analysis; Lipophilicity; Medical sciences; PARAFAC; Partial least squares; Pharmacology. Drug treatments; Principal Component Analysis; Solubility; Thin-layer chromatography; Thin-layer chromatography; Partial least squares; Lipophilicity; PARAFAC; Principal component analysis; Parallel algorithm; Solutes; Determination; Calibration; Thin layer chromatography; Least squares method; Comparative study; Quantitative analysis
• DOI: 10.1016/j.jpba.2010.06.024
• ISSN: 0731-7085; 1873-264X

The lipophilicity of a compound is a fundamental property related to pharmaceutical and biomedical activity. As many approaches are mixed together in every-day published studies, the subject needs some standardization. The paper presents a comparative study on several approaches of TLC lipophilicity determination: a single TLC run, extrapolation of a retention, principal component analysis of a retention matrix, PARAFAC on a three-way array and a PLS regression. All techniques were applied to 35 model solutes with simple molecules, using nine concentrations of six modifiers: acetonitrile, acetone, dioxane, propan-2-ol, methanol and tetrahydrofurane. The elaborated comparative analysis formed several general recommendations. Methanol and dioxane were the best modifiers, while acetonitrile gave the worst and inacceptable correlation of retention with lipophilicity. Surprisingly, good correlations were obtained for the single TLC runs and this method is underestimated in the literature. The advanced chemometric processing proposed recently, such as PCA, PARAFAC and PLS did not show a visible advantage comparing to classical methods. A need to use a robust regression and robust correlation measures, due to presence of significant outliers, was also noticed and studied.