Capillary electrophoresis process

Enantioresolution in capillary electrophoresis (CE) is typically achieved with the help of chiral additives dissolved in the background electrolyte. A number of low as well as high molecular weight compounds such as proteins, antibiotics, crown ethers, and cyclodextrins have already been tested and optimized. Since the mechanism of retention and resolution remains ambiguous, the selection of an additive best suited for the specific separation relies on the one-at-a-time testing of each individual compound, a tedious process at best. Obviously, the use of a mixed library of chiral additives combined with an efficient deconvolution strategy has the potential to accelerate this selection. 

At present moment, no generally feasible method exists for the large-scale production of optically pure products. Although for the separation of virtually every racemic mixture an analytical method is available (gas chromatography, liquid chromatography or capillary electrophoresis), this is not the case for the separation of racemic mixtures on an industrial scale. The most widely applied method for the separation of racemic mixtures is diastereomeric salt crystallization [1]. However, this usually requires many steps, making the process complicated and inducing considerable losses of valuable product. In order to avoid the problems associated with diastereomeric salt crystallization, membrane-based processes may be considered as a viable alternative. 

Capillary electrophoresis offers several useful methods for (i) fast, highly efficient separations of ionic species (ii) fast separations of macromolecules (biopolymers) and (iii) development of small volume separations-based sensors. The very low-solvent flow (l-10nL min-1) CE technique, which is capable of providing exceptional separation efficiencies, places great demands on injection, detection and the other processes involved. The total volume of the capillaries typically used in CE is a few microlitres. CE instrumentation must deliver nL volumes reproducibly every time. The peak width of an analyte obtained from an electropherogram depends not only on the bandwidth of the analyte in the capillary but also on the migration rate of the analyte. 

On the other hand, the most severe constraint of CL analyses is their relatively low selectivity. One major goal of CL methodologies is thus to improve selectivity, which can be accomplished in three main ways (1) by coupling the CL reaction to a previous, highly selective biochemical process such as an immunochemical and/or enzymatic reaction (2) by using a prior continuous separation technique such as liquid chromatography or capillary electrophoresis or (3) by mathematical discrimination of the combined CL signals. This last approach is discussed in Sec. 4. 

Some coupled systems allow measurement of the main N and P forms (nitrate, ammonia and orthophosphates) [22,27,29], among which is a system based on membrane technology in combination with semi-micro continuous-flow analysis (pCFA) with classical colorimetry. With the same principle (classical colorimetry), another system [30] proposes the measurement of phosphate, iron and sulphate by flow-injection analysis (FIA). These systems are derived from laboratory procedures, as in a recent work [31] where capillary electrophoresis (CE) was used for the separation of inorganic and organic ions from waters in a pulp and paper process. Chloride, thiosulphate, sulphate, oxalate,... 

Instrumental resolution, 23 132 Instrumentation. See also Instruments calibration of, 21 161 capillary electrophoresis, 4 633 composition measurement, 11 785 for fermentation, 11 36—40 flow rate, 11 781-783 flow visualization, 11 785-786 fluid mechanics, 11 781-786 food processing, 12 87-88 gas chromatography, 4 611 6 413-414 infrared spectroscopy, 14 225-228 23 137-138... 

III. CAPILLARY ELECTROPHORESIS IN THE DRUG DEVELOPMENT PROCESS, FROM CANDIDATE SELECTION TO THE MARKET... 

This chapter will focus on the potential fields of capillary electrophoresis (CE) used in the development process of drags. Challenges, appropriate remediation to overcome limitations, as well as the benefits will be addressed and described. 

As a result of the pharmacopoeial harmonization process, general chapter 2.2.47. of the Ph.Eur. and general chapter 8 of the JP (Capillary Electrophoresis) and general chapter < 1047) of the USP (Biotechnology-Derived Articles — Tests, Capillary Electrophoresis ) have been harmonized to a major extent. At present some minor differences exist between the text and a few equations in the pharmacopoeia. In these chapters, the following definition of CE is given ... 

Sunday, B. R., Sydor, W., Guariglia, L. M., Obara, J., and Mengisen, R. (2003). Process and product monitoring of recombinant DNA-derived biopharmaceuticals with high-performance capillary electrophoresis./. Capillary Electrophor. 8, 87—99. 

Riekkola, M. L., and Wiedmer, S. K. (1997). Potential of capillary electrophoresis with micelles or chiral additives as a purity control method in pharmaceutical industry. Process Control Qual. 10, 169-180. 

Johnson, B. D., Crinberg, N., Bicker, C., and Ellison, D. (1997). The quantitation of a residual quaternary amine in bulk drug and process streams using capillary electrophoresis. J. Liq. Chromatogr. Related Technol. 20, 257—272. 

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