Chiral Drugs By Capillary Electrophoresis

The separation of enantiomers of drugs is an important subject of research especially in the pharmaceutical field. Because of the similar Physico- Chemical properties of two enantiomers, the separation becomes more difficult. Capillary electrophoresis (CE) has manifested its versatility and potential in the separation of chiral drugs, because of its high efficiency, rapid analysis, low cost, wide range of separation modes and very low consumption of buffer and samples etc. Successful chiral separation lies in choosing accurate chiral selector. Current research is still focus on finding and synthesizing new chiral selectors. Cyelodextrins (CD5) including native and derivatized CDs are among the widely used chiral additives in CE. However, there are some limits to the native CDs in their solubility and physico-chemical properties for chiral separation. CD derivatives exhibit different properties compared to the native ones in the following: 1. Improved solubility; 2. Possibility for different bonds with analytes that can improve the inclusion-eomplexation; 3. The charged CDs can separate uncharged and charged chiral drugs. In the inclusion-complexation mechanism the compound fits the CD cavity with the whole molecule or with the hydrophobic part and, thus, the CD type has a very important role in the separation process. The hydrophobic interaction with the cavity alone is not suffient to enable the separation of chiral drugs; weak bonds between substituent groups on the asymmetric center of analytes and secondary and/or primary groups of CD ring are responsible for chiral recognition. So the chiral separation using CDs derivatives is one of the challenging subject. In chapter one, the development of chiral separation by CE was reviewed, including theoretical studies, applications and different operating models. In chapter two, P 桟D was modified on the 2梙ydroxyl position, mono-2- O-Acetonyl-2-O-hydroxypropyl- P -CD was systhesized. This derivative possesses a deeper cavity and becomes flexibility because of the enlargement 1/- VIII Abstract of the side ring. So it can easily encapture the analyts to form Inclusion- complexation. Meanwhile, because of the exist of carbonyl group the density of electron atmosphere around the side ring is stronger, this increases the interaction between the analytes and CD derivative. Complicated interaction between chiral selector and chiral drug leads to the separation of chiral drug, the modified group is complex, its interaction with the analyts is also complex. All the factors described above are benificial to the separation of the chiral drugs. 15 chiral drugs, such as Econazoleb (Rs:0.86), Ketamine (Rs: 1.53) Benzhexol (Rs:1 .09), Propranolol (Rs:1 .00), Chloroquine (Rs:1 .21), Isoprenaline (Rs: 1.29), Propafenone (Rs:2.20), Verapamil (Rs:0.98), Promethazine (Rs:2 .01), Lobeline (Rs: 1.75), Pemoline (Rs:2.56), Adrenaline (Rs:2.01), Mexiletine (Rs:1.65), Atropine (Rs:1.50), Ketoconazole (Rs:1.61), are separated while only 6 chiral drugs such as Mexiletine (Rs: 1.05), Lobeline (Rs:2.12), Adrenaline (Rs:0.78), Verapamil (Rs:O.48), Bupivacaine (Rs:0.76), Isoprenaline (Rs: 1.83), were separated by DM- $ 桟D. We demonstrated the strong separating ability of 2-O-acetonyl-2-O-h...