In many health related fields the resolution and structural identification of enantiomeric compounds are necessary steps for studying racemic drug interactions. The coupling of capillary electrophoresis (CE) to mass spectrometry (MS) using conventional micelles [above the critical micelle concentration (CMC)] is very difficult if not impossible. Preliminary data in our laboratory indicates that the uses of polymerized surfactant or micelle polymers provide one possible solution for this difficult coupling. This is because of many positive attributes of micelle polymers which includes zero CMC, lower surface activity, low volatility and function as suitable separation media even at lower concentrations of pseudophases. These are some benefits that produce a stable electrospray. This proposal is aimed at synthesis and development of new class of chiral anionic and cationic micelle polymers for use in chiral electrokinetic chromatography (EKC)-MS. Depending on the polarity of the chiral analytes two different approaches are proposed for the success of chiral EKC-MS. The first approach involves simply the use of chiral micelle polymers as additives in EKC-MS or partial-filling EKC-MS for the separation of very polar and charged compounds. For the chiral separation and MS detection of very hydrophobic and neutral chiral molecules that have large capacity factors and low ionization efficiency, a second approach is proposed. This involves the use metal complexes of anionic micelle polymers as reagents for the coupling of ligand exchange-EKC to coordination ion mass spectrometry. The combined use of metal with chiral micelle polymers will not only provide faster and efficient chiral separations of hydrophobic molecules but will also help in efficient transport of complexes to the gas phase for electrospray ionization. In addition, a dual chiral selector system, capillary electrochromatography (CEC)-EKC-MS is also proposed for analytes with multiple chiral centers. Following studies on the optimization of chiral EKC-MS of wide variety of chiral compounds, two different methods will be developed to improve the concentration sensitivity of CE-MS. The first methodology includes a new approach in developing an automated capillary isotachophoresis in conjunction with chiral EKC to improve the sample loadability of the chiral analytes which will benefit analysis of chiral metabolites at therapeutic levels without sample preparation. Besides this, a second methodology involves investigation on chiral EKC-MS-MS for trace level detection and understanding of the metabolic pathways of patients undergoing warfarin and thalidomide therapy for various diseases. We realize that the application of this valuable technology of chiral EKC-MS and chiral EKC-MS-MS will lead to the significant advances across several scientific disciplines. The strategies described in this proposal may signal a new beginning of a highly efficient and information rich hyphenated technology, which will enable our research group and others to acquire significant high throughput screening methods for analysis of chiral drugs than ever previously experienced.
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