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Recent American Food and Drug Administration guidelines have effectively determined that mixtures of chiral compounds can no longer be brought to the pharmaceuticals marketplace. These guidelines require a means for chiral detection and compound separation. This article describes separation and detection of chiral pharmaceuticals using HPLC with circular dichroism detection. Two over-the-counter (OTC) medications, Prilosec and naproxen sodium, along with the prescription drugs Naproxen, Nexium, and Coumadin were analyzed using HPLC with CD, UV, and optical rotation (OR) detection. In all cases the CD and UV detectors displayed a much greater sensitivity than the OR detector. Although in many cases the UV detector did have a slightly better sensitivity than the CD detector, the CD detector had the advantage of only responding to the chiral compounds, eliminating the possibility of interference with the peaks of interest. KEY WORDS: chirality; separation; chromatography; drugs; detection In the early 20th century the relevance of chirality to the pharmaceutical industry was established by the fact that one enantiomer of hyoscyamine possessed greater pharmacological activity than the other. Today, most new drugs and those under development consist of a single optically active isomer, and chirality is also becoming an issue for the agrochemical and other industries. Regulatory agencies throughout the world are currently reviewing the importance of chirality with regard to pharmaceutical and agrochemical products. New guidelines from such agencies have been key drivers for the focus on single enantiomer products in these industries.There are many chiral issues in drug development. Racemic drugs can cause problems because of the differences not only in the biological effects but also in the pharmacokinetics of the enantiomers. One example is Perhexiline, a drug used to treat abnormal heart rhythms. In the 1980s the racemate killed a number of people who had accumulated gram quantities of the enantiomer that was more slowly metabolized. If researchers had realized that one enantiomer had a much longer half-life, they might have come up with a drug with just the fast-clearing enantiomer. It was one of the very early examples where an understanding of chirality in drugs is critical. 1 At present, a number of chiral switches are still in the pipeline. What is likely to increase is the development of single enantiomers of a chiral compound for different therapeutic uses, as exemplified by the dextromethorpan/ levomethorpan dichotomy. Examples include the work on methylphenidate (Ritalin), a drug to treat attention deficit hyperactivity disorder (ADHD). Methylphenidate has two chiral centers and the drug is a racemate of the S,S and R,R isomers. Natural products present another fertile field for discovering therapeutic properties of single enantiomers. Recent studies of the enantiomers of natural products or semisynthetic drugs derived from natural products indicate that they could have distinct therapeutic value. F...

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