Determination Of Octanol Water Partition Coefficients By Microemulsion Electrokinetic Chromatography Based On Peak-Shift Assay

In conventional microemulsion electrokinetic chromatography (MEEKC), a series of reference compounds and the migration time of microemulsion phase are required to determine the octanol-water partition coefficient (logP_o/w) of compounds. The accuracy of the obtained logP_o/w is depended on the correctness of the logP_o/w of reference compounds and the migration time of microemulsion phase. Thus, a novel MEEKC method based on peak-shift assay (p-s MEEKC) was developed to measure logP_o/w value of compounds. Here, a series of microemulsion electrolytes with gradient content of microemulsion droplets were employed. And the logP_o/w value of compounds could be calculated according to the changes in effective mobility of analyte as a function of the amount of microemulsion droplets in the electrophoresis electrolytes. Based on this, the logP_o/w value of compounds and drugs were studied. Then, the use of microemulsion composed of nonionic surfactant to determine the logP_o/w value of charged compounds was proposed. Moreover, relative mobility substitited for mobility was developed to describe the migration of analytes and used to estimate the hydrophobicity of drugs.In this thesis, the main research work and obtained results are as follows:â‘ According to the changes in effective mobility of analyte as a function of the amount of microemulsion droplets, a novel MEEKC method based on peak-shift assay (p-s MEEKC) was developed. Then, the relationship between the concentration of analytes and effective mobility was investigated. Furthermore, the logP_o/w of p-nitroaniline was studied to prove the reliability of the method.â‘¡The logP_o/w values of 11 compounds were determined using the proposed p-s MEEKC and conventional MEEKC method. Then, the determined values by the two methods were compared with reference value. It is showed that the logP_o/w values obtained by the developed p-s MEEKC were more accurate. In addition, the errors of the determined value by p-s MEEKC were analysed and the applicability of the new method was investigated.â‘¢To reduce the electrostatic interaction between the charged compounds and negative microemulsion droplet composed of sodium dodecyl sulfate (SDS), a nonionic surfactant named tween-80 was used to prepare microemulsion electrolyte. Then the tween-80 microemulsion was applied to determine the logP_o/w values of some charged compounds. â‘£This work evaluates the use of relative mobility to estimate logP_o/w of drugs using p-s MEEKC. The logP_o/w of 5 compounds were determined by the use of relative mobility and compared with the results obtained by the use of absolute mobility. Furthermore, the developed method was applied to determine the logP_o/w values of 3 drugs. The result shows that the errors caused by the change of the viscosity and the fluctuation of applied voltage, current and temperature in the experiment could be avoided by the use of relative mobility to descript the analyte migration in MEEKC.The results showed that the logP_o/w values obtained by the p-s MEEKC were comparable to literature values and those determined by the conventional MEEKC method. It is justified that the p-s MEEKC method was an acceptable method for evaluation hydrophobicity of compound. In the developed method, the proper reference compounds which were difficult to obtain in many cases as well as the errors caused by the use of literature logP_o/w values were avoided. The proposed p-s MEEKC method is an alternative method for the determination of logP_o/w value, and offers a new way for the determination of logP_o/w value without of the reference compounds.