ON THE PRECISE ESTIMATION OF R(M) VALUES IN REVERSED-PHASE THIN-LAYER CHROMATOGRAPHY INCLUDING ASPECTS OF PH-DEPENDENCE

In order to improve the application of reversed-phase thin-layer chromatography (RP-TLC) for the chromatographic estimation of drug lipophilicity, some aspects of measuring true R(M) values [log (1/R(F) - 1)] are considered in the present investigation: (1) An optimization of experimental conditions, including the importance of temperature and humidity, as well as densitometric evaluation of spots is presented. (2) The estimation of thermodynamically true R(M) values is described; it is shown that in case of high modifier contents preloading effects induce pronounced deviations of R(F) from R(F)' values. Only the latter allow the calculation of true R(M) values. (3) The influence of solvent pH on R(M) values is negligible for pure partition chromatography in the case of low modifier contents; with increasing modifier contents polar adsorption becomes more prominent; under these conditions an influence of pH on R(M) in the case of strong bases is detected.