Chromatographic Determination of Lipophilicity of Potential Antitrypanosomal Compounds.

RAVIOLO, MÓNICA A., BRIÑÓN, MARGARITA C., GUALDESI, MARÍA S., PERIS-VICENTE, J., CARDA-BROCH, SAMUEL, ESTEVE ROMERO, JOSEP S.

Simposio; 39th International Symposium of High-Performance Liquid Phase and Related Techniques.; 2013

Lipophilicity of a substance is one of the parameters which plays a basic role in biological processes. Fujita et al have proposed the n-octanol/water partition coefficient, Po/w, as a measure of compound’s lipophilicity. It has been demonstrated that the capacity factor (k) of a compound obtained by RP-HPLC is an indirect reliable descriptor of lipophilicity of a compound. Moreover, the k which is extrapolated from the binary phase to 100% water, log k’w, is an even better descriptor of lipophilicity because it is independent of any organic modifier effects. This method was extensively evaluated and the Organization for Economic Cooperation and Development (OECD) to prepare a guideline that should be followed to produce reliable log Po/w values using RP-HPLC. According to OECD, the log Po/w value of an analyte can be evaluated from a calibration graph constructed from the log Po/w (bibliography) vs log k’w (experimental) of reference compounds. (High correlation was found r2 = 0.9960). The aim of this study was to determine the log Po/w of four novel derivatives of allopurinol, synthesized as potential antitrypanosomal drugs (etiologic agent of Chagas´ disease). For this purpose we determined the log k’w of these derivatives on a C-18 stationary phase at a flow rate of 1 mL min-1 using different mixtures of methanol and buffer pH 5.5 as eluent and UV detection. The log Po/w of each derivative was obtained, and as expected were more lipophilic that allopurinol, which gives them advantages in terms of pharmacokinetic properties such as cross membranes by passive diffusion.