MEEKC

MEEKC is a CE mode similar to MEKC, based on the partitioning of compounds between an aqueous and a microemulsion phase. The buffer solution consists of an aqueous solution containing nanometer-sized oil droplets as a pseudo-stationary phase. The most widely used microemulsion is made up of heptane as a water-immiscible solvent, SDS as a surfactant and 1-butanol as a cosurfactant. Surfactants and cosurfactants act as stabilizers at the surface of the droplet. 

Similarly to MEKC, strong linear correlations between the logfe measured by MEEKC and the log Pod were reported by several authors as shown in the supplementary material (see Section 13.5). 

Other electrokinetic chromatography techniques using liposomes (LEKC) and vesicles (VEKC) have also been applied for logP d estimation. Liposomes and vesicles are organized structures containing continuous bilayers of monomers enclosing an aqueous core region. 

The logk obtained by MEKC, MEEKC and LEKC were also compared with membrane permeability reference data by Ornskov et al. [92]. An improved correlation was obtained in the order MEKC MEEKC LEKC. Thus, LEKC appears to provide experimental conditions that mimic more closely physiological membranes [93], However, liposomes and vesicles remain unstable and difficult to prepare reproducibly. Their use is then devoted to some parhcular applicahons. 

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MEEKC Microemulsion electrokinetic chromatography TFA Target factor analysis... 

TABLE 5 LogP Values Measured by MEEKC vs. Literature Values... 

Compound Logk (MEEKC) LogP (MEEKC) LogP (literature) ALogP pKa (CE)... 

SDS, octane, borate, butan-l-ol MEEKC system with direct detection Neutral and charged solutes 52... 

The fact that the EP wants to replace old TEC methods with more selective, efficient, and sensitive separation methods provides the chance for the introduction of more CE methods. The continuous development of analytical methods is reflected in the national and international pharmacopoeias. This might be demonstrated for atropine sulfate. Whereas the Deutsches Arzneibuch, 7th Edition (DAB 7) only limits the tropic acid by extraction and titration with NaOH and phenolphthalein indication, the 4th edition of the EP looked for foreign alkaloids and decomposition products by means of TEC with a potassium iodobismuthate for detection. By intensity comparison of the obtained spots, it was possible to limit these impurities to 0.5%. The EP 5 utilizes an ion-pair HPLC method that is able to limit most of the impurities to less than 0.2%. To make the method more robust, an HPLC method using a polar embedded was applied, which might be the next step for the EP. However, recently the same authors have reported on a MEEKC method being as robust and precise as the latter HPLC method (see Eigure 6) but far more sensitive and, therefore, a future perspective for the EP. 

It is clear from the applications described above that the strength of CE in the field of impurity profiling lies in the various selectivities that can be applied. Not only can one take advantage of electrophoretic phenomena but also of the principle of chromatographic separation and partitioning that is present in techniques such as MEKC and MEEKC. The resolution of substances based on size differences as in CGE is also very useful in the field of biopharmaceuticals. CE can be seen as a complementary technique to other commonly used separation techniques as LC, and in view of its capacity to separate large numbers of compounds, it should certainly always be kept in mind when an analytical problem has to be solved. 

Hansen, S. H., and Sheribah, Z. A. (2005). Comparison of CZE, MEKC, MEEKC and non-aqueous capillary electrophoresis for the determination of impurities in bromazepam. /. Pharm. Biomed. Anal. 39, 322-327. 

FIGURE 2 MEEKC APPI/MS analysis of five steroids. Total ion current (TIC) and extracted ion currents (XIC) of gestrinone (GES), canrenone (CAN), metolazone (MET), finasteride (FIN), and dexamethasone (DEX) and an EOF marker (N,N-dimethylformamide, DMF). 

In this section, MEEKC with SDS-heptane-1 -butanol buffer is described as a tool for determination of lipophilicity of drugs. In addition, the comparison between the scale from MEEKC and other scales will be presented. 

For MEEKC, the migration index (MI) scale is quite effective in improving the reproducibility. This was introduced by Muijselaar et al. in MEKC (44) and then modified to extend the range of the migration window of the reference compounds as follows (47) ... 

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