Chiral separation of pharmaceutical compounds by capillary electrophoresis using cyclodextrins.

다국어 초록 (Multilingual Abstract)

Capillary electrophoresis (CE) has proven to be an invaluable tool for chiral separations. Since the introduction of the first commercial CE instrument a decade ago, its applications have become widespread. Today, CE is a versatile analytical technique which is successfully used for the separation of small ions, neutral molecules as well as large biomolecules. The advantages of this method over high-performance liquid chromatography (HPLC), gas chromatography (GC), and gel electrophoresis include high efficiency and fast separations, relatively inexpensive and long lasting capillary columns, small sample size requirements, and low reagent consumption. Herein, the chiral resolution of various model pharmaceutical compounds was investigated using various single-isomer cyclodextrins. The successful coupling of CE to tandem mass spectrometric detection was also explored. Furthermore, the solid-phase extraction of representative compounds was examined in biological matrices.
Chapter 2 reports the use of cyclodextrins as a chiral additive for the enantiomeric separation of model pharmaceutical compounds. Importantly, the impact of derivatized cyclodextrins (CDs) in the background electrolyte (BGE) was critically evaluated.
Chapter 3 investigates the effects of coupling capillary electrophoresis to mass spectrometry (CE-MS). Compatibility factors as well as different interfaces were explored. The combination of these two powerful analytical techniques is especially amenable to the analysis of analytes with limited sample quantities which is frequently important when analyzing biological matrices.
Chapter 4 examines the chiral separation of labetalol with multiple stereogenic centers. Data illustrating the effects of capillary length and cyclodextrin concentration on the separation are presented. The optimized method was applied to the analysis of human control plasma containing labetalol utilizing solid-phase extraction (SPE) in the 96-well format. Similarly, Chapter 5 investigates the use of single-isomer cyclodextrins on the chiral separation of timolol enantiomers in biological matrices by CE-MS.
Finally, in Chapter 6 a library representing chiral separations of model pharmaceutical compounds are reported. The results illustrate the complete profile of selectivity and sensitivity for each compound in the various cyclodextrin BGEs and at various concentrations and pH ranges. The single-isomer CD chiral selectors, heptakis-(2,3-dihydroxy-6-sulfato)-beta-CD (HS-beta-CD), heptakis-(2,3-diacetyl-6-sulfato)-beta-CD (HDAS-beta-CD), and heptakis-(2,3-dimethyl-6-sulfato)-beta-CD (HDMS-beta-CD) all proved to be applicable towards the chiral separation of representative acids, bases, and neutrals. (Abstract shortened by UMI.).