pH Effects in Micellar Liquid Chromatographic Analysis for Determining Partition Coefficients for a Series of Pharmaceutically Related Compounds

Five drugs were studied using micellar liquid chromatography (MLC) to determine micelle-water partition coefficients (P_mw) over a range of mobile phase pH values and column temperatures. In all cases the sodium dodecyl sulphate mobile phase utilised a CN reversed-phase column with UV detection, optimised for the λ_max of each drug. The pH of the mobile phase was systematically varied over the range 3 to 7 pH units, incorporating values above and below the pK_a's of the drugs studied. From this it was possible to determine MLC based values of P_mw and establish their relationships with pK_a values, software predicted partition coefficients (clogP), dissociation constants (logD) and published partitioning data (logP_ow). This study also considered the relationship between column temperature, from 294K to 317K, and P_mw. For all five drugs it was found that P_mw decreased with increasing pH implying a systematic increased preference for the drug to remain in the aqueous phase rather than partition into the micellar phase. In addition, the partition coefficient displayed a linear relationship with log D over the pH range for each drug with a 'break-point' observed at the pK_aa for each drug. With respect to increasing temperature, the results were non-linear indicating that there is no general relationship for these drugs with temperature. Overall, it was found that MLC is suited to the measurement of partition coefficients for pharmaceutical compounds yet it should be noted that both pH and temperature play a significant role in the values obtained.