J. Sep. Sci. 2012, 35, 915–921 915 Dorina Casoni Costel S ˆ arbu Faculty of Chemistry and Chemical Engineering, Babes ¸ -Bolyai University, Cluj-Napoca, Rom ˆ ania Received November 28, 2011 Revised January 5, 2012 Accepted January 17, 2012 Research Article Comprehensive evaluation of lipophilicity of biogenic amines and related compounds using different chemically bonded phases and various descriptors The retention behavior for a series of biogenic amines and related sympathomimetic drugs has been investigated in reversed-phase thin-layer chromatography using RP-2, RP-8, RP- 18W, and Diol stationary phase and mixtures of phosphate buffer (pH = 7.10) and methanol in different proportions as mobile phases. Several methodologies like arithmetic mean of experimental retention values, extrapolation to zero methanol concentration procedure and principal component analysis were applied to retention data values (R M ) in order to de- termine relevant parameters (mean of R M − mR M , R M0 , and scores corresponding to the first principal component − PC1/R M respectively) encoding information on the lipophilic behavior of compounds. High similarities in lipophilicity behavior of investigated amines were highlighted by mR M and PC1/R M lipophilicity indices for all of the studied stationary phases. The experimental results were compared with some computed lipophilicity pa- rameters expressed as distribution coefficients at working pH (logD), partition coefficients (logP N , logP I , and diff(logP N–I )) concerning both neutral and fully protonated species and difference between both species, and also with various lipophilicity values (logP) generated by different commonly used software. Significant correlations were observed between the experimental lipophilicity indices mR M respectively PC1/R M and diff(logP N–I ) values in all cases. Keywords: Biogenic amines / Chemically bonded phases / Computed logP / Lipophilicity / TLC DOI 10.1002/jssc.201101032 1 Introduction It is demonstrated that a successful drug candidate requires not only good pharmacodynamic properties but also a suit- able pharmacokinetic profile. In drugs pharmacokinetic, par- tition and distribution coefficient (logP and logD) are key parameters for the in vitro metabolic and binding data [1–3]. The in vivo process involves partitioning between aqueous media and biological membranes as gut wall or blood–brain barrier. Generally, the affinity of a compound for biological membranes may be represented by its lipophilicity [4] de- fined by IUPAC as “the affinity of a molecule or a moiety for a lipophilic environment”. Since the introduction of the Han- sch approach [5] to drug design, the lipophilicity of drugs and general chemicals gained great importance, its study re- vealing a wealth of information on intermolecular forces, intramolecular interactions and molecular structure in the Correspondence: Associate Professor Dr. Costel S ˆ arbu, Faculty of Chemistry and Chemical Engineering, Department of Analytical Chemistry, Babes ¸-Bolyai University, Street Arany Janos 11, RO- 400028, Cluj-Napoca, Rom ˆ ania E-mail: csarbu@chem.ubbcluj.ro Fax: +40-264-590818 broadest sense. Also, this particular property is known to be important for the in vivo distribution of organic compounds [6] (by influencing their solubility, oral absorption, cell uptake, blood–brain penetration, and metabolism) and to rational- ize a number of biological events as membrane penetration and permeability [7]. Usually, the lipophilicity of a compound can be quantitatively characterized by the logarithm of n- octanol/water partition coefficient (logP) or distribution co- efficient (logD) if ionized molecular species are present. The traditional experimental method for determining logP is the shake flask one but reliable and fast chromatographic ap- proaches have been developed also [8–14]. Reversed-phase chromatographic techniques, in particular high performance liquid chromatography (RP-HPLC) and thin layer chromatog- raphy (RP-TLC) have proved to well simulate octanol–water partitioning and they are becoming very popular alternatives for lipophilicity assessment. In most of cases, the lipophilic- ity values measured by liquid chromatography (LC) and thin- layer chromatography (TLC) were generally well correlated [15]. In addition, the determination of lipophilicity by RP- TLC is rapid and needs no sophisticated instrumentation. In recent years, RP-TLC technique has been used to esti- mate the lipophilicity of a considerable number of molecules [16–20] and the relationship of this property with biological C  2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.jss-journal.com