Determination of logPo/w using a chromatographic method — ASN Events

Determination of logPo/w using a chromatographic method (#138)

Josep Esteve-Romero 1 , Monica-Ana Raviolo 2 , Margarita Briñon 2 , Maria S. Gualdesí 2 , Juan Péris-Vicente 1 , Samuel Carda-Broch 1 , Enrique Ochoa-Aranda 3
  1. Química Bioanalítica - QFA - ESTCE, Universitat Jaume I, Castelló, La Plana, Spain
  2. Departamento de Farmacia, Universidad Nacional de Córdoba, Córdoba, Argentina
  3. Biopatologia Molecular, Hospital Provincial, Castelló de la Plana, Spain

The n-octanol/water partition coefficient, Po/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 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 vs log kw (experimental) of reference compounds. High correlation was found r2 = 0.9960. In our laboratory, we determine the log Po/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 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.

 

 

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.