ABSTRACT
At the beginning of the twentieth century, Abderhalden and Muller [1,2] reported the rst observed difference in pharmacological activity for the two enantiomers of a drug. They found that (S)-adrenaline and (R)-adrenaline had different effects on the blood pressure of laboratory animals. Today, it is well known that the individual enantiomers of a drug often have different pharmacokinetic and pharmacological properties, as their target structures in the human body are chiral, as they also are in animals. There is a broad range of examples in which the enantiomers of drugs show differences in their bioavailability, distribution, receptor interaction, and metabolic and excretion behavior, and, thus, they should be considered to be two different compounds [3]. It has also been proven that the use of a single enantiomer may reduce the dose of a drug, simplify the dose-response relationship, and minimize the toxicity caused by the therapeutically less-active enantiomer [3]. The guidelines issued by authorities for the registration of new drugs state that a chiral impurity should be treated in the same way as any other impurity, and an enantioselective determination should be included in the specication of enantiomerically pure drugs [4,5]. The trend in drug discovery is toward single enantiomers. Fifty percent of the drugs approved by the U.S. Food and Drug Administration between 2000 and 2002 were single enantiomers, 6% racemates and 44% achiral [6]. That is a signicant increase since 1983, when 37% of the new drugs that were registered worldwide were racemates and only 26% were single enantiomers (37% were achiral) [6]. The progress toward enantiomerically pure drugs makes the selective and rapid analysis of enantiomers an important issue in drug development, especially for chiral purity determinations of the lead
17.1 Introduction ..........................................................................................................................507 17.1.1 Need for Chiral Pharmaceutical Analysis ................................................................507 17.1.2 Separation of Enantiomers by HPLC .......................................................................508
