Chiral Drug Separation By Binary Cyclodextrin Systems And The Chiral Drug Separation Database

The individual enantiomers of chiral drugs owe different pharmacological and toxicological properties. Capillary electrophoresis has recently become a preferred technique in chiral separation. Binary cyclodextrin (CD) systems are good at analyzing compounds of enantiomeric solutes at many instances, moreover their mechanisms are not always the same as single CI) ones, thus many attractive and intriguing issues have been focused on them in separation science. In this thesis, the selectivity of sulfated-f3-cyclodextrin (S-J3-CD) was compared with the ones of seven other neutral CDs, and the separation mechanism of binary CD systems containing one of neutral CDs and S-f~-CD for separating two category of 14 drugs were systematically studied. Moreover, based on information of chiral drug separation from the work of this group and the data from literature, a useful chiral drug separation database was setup. In the first part of the thesis, the resolution of seven cardiovascular drugs separated by S-{~-CD and seven other neutral CDs were compared. The results show that S-fl-CD has more sensitive enantiomer selectivity and higher separation effect than that of any one of those neutral CDs. When binary CD systems containing of S-13-CD and Heptakis(2,3 -di-O-methyl)-~3-cyclodextrin (DM-13-CD) was used, the separation results were quite different. A ternary complex electrophoresis model was introduced based on the structures of drugs to explain the changes of migration time and the resolutions of the enantiomers of gallopaml and carvedilol. Chiral separation of~-block antagonists, a kind of drugs which are similar both in their fi.inctions and in their structures in binary CD systems was systematically studied. a-CD and y-CD were added respectively to the buffer containing S..f3-CD, the influences on the resolution were completely different, t - though neither of the natural CD has eriantionier selectivity to the drugs. Binary systems of S-n-CD with derivative and natural CD were compared, on the whole, derivative CDs are superior to natural ones. Competitive mechanism and consideration of mobility change are introduced to explain the above phenomena and the variety of migration time as well. In the last part of the thesis, a chiral drug separation database was setup based on the information from the accumulation of our group and data from literature. K present, we have collected more than 600 chiral drugs with foundational information such as molecular formula, ~ructure, main function etc., 3nloIig those the separation information of more than 400 of the drugs were includei, which might be quite usefi.ul for the research and applications of chiral drug separation in the coming years.