Chiral drugs, development techniques

Enantiomers are distinguished on the basis of their interaction with a chiral selector. Development of chiral selectors or chiral stationary phases (CSPs) for GC, HPLC, and CE has rapidly opened a new dimension in the area of chiral drug separation techniques. There are different chiral selectors available for enantiomeric separation of drugs and pharmaceuticals. Finding a suitable chiral selector, whether immobilized on a solid support (GC, HPLC) or added to a running buffer (HPLC, CE), is still often based on trial and error. A few predictions can be made, however, if common structural elements are present. After a selector has been chosen, variables, such as the nature, ionic strength, and pH of buffer, can be varied, as can presence of organic modifiers, temperature, and so on. 

In paying credit to the fact that the SMB is the most promising chromatographic technique for the production of enantiomerically pure chiral drugs, this technique is discussed below in a rather comprehensive way. Together with the principles, some strategies of method development are also addressed. 

More than half of small druglike molecules are chiral. The Food and Drug Administration (FDA) requires testing of pure enantiomers. Such testing is most useful early on in drug development. SFC is dramatically superior to HPLC for chiral separations. SFC offers dramatically faster method development and should be the technique of choice for any molecules soluble in organic solvents (i.e., most druglike molecules). Further, unlike capillary electrophoresis, SFC is fully scalable. A method developed at the analytical scale should work equally well at the semiprep level. 

Direct HPLC enantioseparation techniques, which are free of many disadvantages of GC, indirect and chiral mobile phase HPLC methods, have gained unequivocal prevalence in bio-analytical studies. Several methods have been advanced so much that they allow enantiose-lective determination not only of the parent chiral drugs but also of their pharmacologically relevant metabolites [121]. As already mentioned above, a direct injection of biofluids offers several advantages in terms of analysis time and sample recovery. Precolumns packed with achiral or chiral packings, or with the recently developed so-called restricted-access packing materials, may be useful in this case. 

Professor Aboul-Enein is a member of the World Health Organization (WHO) advisory panel on international pharmacopeia and pharmaceutical preparations, and he is a Fellow of the Royal Society of Chemistry (UK). He received his B.Sc. degree (1964) in pharmacy and pharmaceutical chemistry from Cairo University, Cairo, Egypt, and his M.Sc. (1969) and Ph.D. (1971) degrees in pharmaceutical and medicinal chemistry from the University of Mississippi, Oxford, USA. Professor Aboul-Enein s current research interests are in the field of pharmaceutical and biomedical analysis and drug development, with a special emphasis on chiral chromatography, ion-selective electrodes and other separation techniques. 

---