The n-octanol/water partition coefficient, P_o/w, is 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 P_o/w values using RP-HPLC. According to OECD, the log P_o/w value of an analyte can be evaluated from a calibration graph constructed from the log P_o/w vs log k’_w (experimental) of reference compounds. High correlation was found r² = 0.9960. In our laboratory, we determine the log P_o/wof 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 P_o/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.

Acknowledgments: This work was supported by Projects Res. Nº 162/12 of Secretaria de Ciencia y Técnica – UNC and P1.1B2012-36 of Pla de Promoció de la Investigació de la Universitat Jaume I.