The overall hypothesis of this research stems from our belief that polymers of chiral surfactants (aka. molecular micelles) provide better separation and detection in capillary electrophoresis-mass spectrometry (CE-MS) than conventional (unpolymerized) micelles. In addition, it also provides sensitive MS detection compared to any existing low molecular weight chiral selectors (cyclodextrins, macrocyclic antibiotics, unpolymerized surfactants). This hypothesis is based upon previous CE-MS strategies developed in our laboratory for enhanced separation and MS detection of chiral molecules. Furthermore, we have progress report and preliminary data provided in this proposal, which clearly support this hypothesis. Thus, the overall goal of this R01 application is to expand the scope of polymers of chiral surfactant to develop better, faster, rugged and in particular even more sensitive as well quantitative method for chiral analysis to meet the needs in life sciences, medicine and biotechnology. Three different aims are suggested for this research.
The first aim i nvolves synthesis and development of several novel classes of anionic and cationic molecular micelles that have zero CMC, low surface activity, function as pseudophases over a wide range of concentrations and pH as well as provide stable electrospray for micellar electrokinetic chromatography-mass spectrometry (MEKC-MS). Two additional significant advantages of molecular micelles are that they form very stable microemulsions and very homogenous molecularly imprinted nanoparticles (resulting in no peak tailing of the second eluting enantiomer). Utilizing the former advantage, we propose to develop microemulsion polymers (polymerized with volatile co-surfactant and oil) or micelle polymers dissolved in volatile microemulsion buffers, which could be very beneficial to the analysis of very hydrophobic chiral molecules. In addition, the latter advantage could effectively be utilized for ultrafast analysis of enantiomers in CE-MS. The second component of the proposed research involves the development of novel surfactant-based monolithic columns for CEC-MS.
This second aim builds upon expertise that we have developed under first aim on the synthesis of chiral surfactant monomers. In particular, CEC-MS will be used for the separation of several classes of short chain or polar anionic, cationic and neutral chiral compounds that are difficult to separate by MEKC-MS.
The third aim i nvolves developing novel applications of chiral MEKCMS/ MS for trace level detection and quantitation of warfarin metabolites in patients undergoing warfarin therapy. In addition, MEKC-MS/MS will also be applied to study dextromethorphan metabolism in urine to distinguish between the users and abusers of this enantiomeric drug.
Chiral separations are very important for developing pure, safe and affordable pharmaceutical drug, which affect human health. We proposed to develop novel molecular micelles and monolithic phases, which can measure these enantiomeric drugs in biological samples based on powerful separation techniques of capillary electrophoresis and very sensitive mass spectrometry methods. We propose to test these methodologies by analyzing the metabolism of drugs in patient samples with various metabolic diseases.
|Liu, Yijin; Wu, Baolin; Wang, Peng et al. (2016) Synthesis, characterization, and application of polysodium N-alkylenyl ?-d-glucopyranoside surfactants for micellar electrokinetic chromatography-tandem mass spectrometry. Electrophoresis 37:913-23|
|Liu, Yijin; Jann, Michael; Vandenberg, Chad et al. (2015) Development of an enantioselective assay for simultaneous separation of venlafaxine and O-desmethylvenlafaxine by micellar electrokinetic chromatography-tandem mass spectrometry: Application to the analysis of drug-drug interaction. J Chromatogr A 1420:119-28|
|Lu, Yang; Shamsi, Shahab A (2014) Comparison of positively and negatively charged achiral co-monomers added to cyclodextrin monolith: improved chiral separations in capillary electrochromatography. J Chromatogr Sci 52:1109-20|
|Liu, Yijin; Shamsi, Shahab A (2014) Combined use of chiral ionic liquid surfactants and neutral cyclodextrins: evaluation of ionic liquid head groups for enantioseparation of neutral compounds in capillary electrophoresis. J Chromatogr A 1360:296-304|
|Bragg, William; Shamsi, Shahab A (2013) High Throughput Analysis of Chiral Compounds Using Capillary Electrochromatography (CEC) and CEC-Mass Spectrometry with Cellulose Based Stationary Phases. Sep Sci Technol 48:2589-2599|
|Wang, Xiaochun; Davis, Ian; Liu, Aimin et al. (2013) Development of a CZE-ESI-MS assay with a sulfonated capillary for profiling picolinic acid and quinolinic acid formation in multienzyme system. Electrophoresis 34:1828-35|
|Wang, Xiaochun; Davis, Ian; Liu, Aimin et al. (2013) Improved separation and detection of picolinic acid and quinolinic acid by capillary electrophoresis-mass spectrometry: application to analysis of human cerebrospinal fluid. J Chromatogr A 1316:147-53|
|Wang, Xiaochun; Hou, Jingguo; Jann, Michael et al. (2013) Development of a chiral micellar electrokinetic chromatography-tandem mass spectrometry assay for simultaneous analysis of warfarin and hydroxywarfarin metabolites: application to the analysis of patients serum samples. J Chromatogr A 1271:207-16|
|He, Jun; Shamsi, Shahab A (2013) Application of polymeric surfactants in chiral micellar electrokinetic chromatography (CMEKC) and CMEKC coupled to mass spectrometry. Methods Mol Biol 970:319-48|
|Bragg, William; Shamsi, Shahab A (2012) A novel positively charged achiral co-monomer for ?-cyclodextrin monolithic stationary phase: improved chiral separation of acidic compounds using capillary electrochromatography coupled to mass spectrometry. J Chromatogr A 1267:144-55|
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