Study On Microemulsion Electrokinetic Chromatography For Hydrophobicity Of Pharmaceuticals

Microemulsion electrokinetic chromatography (MEEKC) has been used as a powerful method for indirect measuring the hydrophobic parameters (logP_ow) of various kinds of compounds. In order to obtain a correct value, the migration time of the solute (t_m) in MEEKC must be accurately required, because the t_m is an important parameter in measuring hydrophobicity with MEEKC. However, in our studies on conventional MEEKC, the influence of concentrations, injection volumes of compounds and high electric-field on their migration behavior was found, which may bring some problems when determining the logP_ow values. Therefore, an improved MEEKC is expected to be established to ensure the accuracy of t_m, which can obtain more accurate logP_ow values.In this paper, an improved method of MEEKC (I-MEEKC) that can solve the problems of determining logP_ow by conventional MEEKC was developed, In addition, a new method of MEEKC without microemulsion phase marker was studied. In this method, the migration time of microemulsion phase (t_me) was obtained by multiline fitting program, which can avoid the error from tracing t_me.The preparation process, feasibility and reliability of I-MEEKC were studied in detail and several applications with satisfactory results were performed. The main research and results are listed below:1. A novel method of MEEKC (I-MEEKC) was established, and its feasibility and reliability were studied. The concentrations, injection volumes of 5 anilines and high electric-field impacting on their migration behavior were studied. The reason and mechanism were also studied. Based on the study above, the I-MEEKC method was then developed. The logP_ow values of benzene, toluene, ethyl benzene, acilovir and acetaminophen by I-MEEKC were obtained: the average error between logP_ow values estimated using I-MEEKC and the ones from literature was 0.16 logarithm units.2. The migration time of microemulsion phase (t_me ) was obtained by non-linearity fitting with logP_ow, values from literature and measured migration time (t_m) of a series of organic compounds, a calibration curve for estimating logP_ow of pharmaceuticals was thus set up. The logP_ow values of 4 pharmaceuticals that are electric neutral measured by this method were close to those determined by shake-flask method, and the average error between values from two methods was 0.15 logarithm units. Furthermore, according to the suggested theory, the measurement accuracy of logP_ow is correlated...