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

Laura      J. Waters; Yasser      Shahzad; John      C. Mitchell

Abstract

Five drugs were studied using micellar liquid chromatography (MLC) to determine micelle-water partition coefficients (Pmw) 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 λmax 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 pKa‘s of the drugs studied. From this it was possible to determine MLC based values of Pmw and establish their relationships with pKa values, software predicted partition coefficients (clogP), dissociation constants (logD) and published partitioning data (logPow). This study also considered the relationship between column temperature, from 294K to 317K, and Pmw. For all five drugs it was found that Pmw 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 pKa 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.

Keywords: HPLC, logP, Micellar Liquid Chromatography, MLC, partition coefficients, pH, CMC, physicochemical property, aromatic hydrocarbons