Pharmaceutical industry chiral drug

Methods development for chiral analyses has been one of the most challenging separation problems for the analytical chemist in the pharmaceutical industry. Racemic drug substances have a variety of chemical structures and several chiral selectors are available for the analyst to choose in order to obtain the enan-tioselectivity needed for chiral resolution. To alleviate this problem, a fast capillary electrophoresis procedure for the enantiomeric separation of acidic and basic compounds using native and modified cyclodextrins has been described (200). The technique is called cyclodextrin array chiral analysis. A generalized optimi-... 

Chirality plays a major role in the development of drugs. A chiral molecule is defined as nonsuperimposable on its mirror image. Two chiral molecules commonly called enantiomers are often compared to the right and left hands. The same type and number of atoms are in the two enantiomers but the spatial arrangement of atoms is different Usually one enantiomer is preferred over the other. In the pharmaceutical industry chiral molecules constitute a large portion of pharmaceutical sales. More than half the drugs approved worldwide are chiral. Examples include Lipitor and Zocor , as well as ibuprofen sold under the common brand names Motrin and Advil . 

The availability of a new class of efficient separations technology for chiral drugs can have an impact on other business issues now at the forefront of the pharmaceutical industry. For example, the strategy of better drug life cycle management can be... 

It was apparent that the FDA recognized the ability of the pharmaceutical industry to develop chiral assays. With the advent of chiral stationary phases (CSPs) in the early 1980s [8, 9], the tools required to resolve enantiomers were entrenched, thus enabling the researcher the ability to quantify, characterize, and identify stereoisomers. Given these tools, the researcher can assess the pharmacology or toxicology and pharmacokinetic properties of enantiopure drugs for potential interconversion, absorption, distribution, and excretion of the individual enantiomers. 

The Japanese regulatory authority is the Ministry of Health and Welfare (MHW) and the Pharmaceutical and Medical Safety Bureau (PSMB) is responsible for the promulgation of national and international guidelines in the form of Notifications. Guidelines are available on the Internet web-site of the National Institute of Health and Science (http //www.nihs.go.jp). The MHW has not issued specific guidance on the development of chiral drugs, but has nonetheless responded to the enantiomer-versus-racemate scientific debate. The attitude of the MHW and its advisory body, the Central Pharmaceutical Affairs Council (CPAC) is discussed in two articles by Shindo and Caldwell published in 1991 and 1995 [17, 18]. The latter paper analyzes the results of a survey of the Japanese pharmaceutical industry which sought responses on chirality issues. 

Caldwell, J., (1995) Regulation of Chiral Drugs, Pharmaceutical News, 2, 22-23. Caldwell, J. (1995) Chiral Pharmacology and the Regulation of New Drugs, Chem. and Industry, 5, 176-179. 

Of much recent interest to the pharmaceutical industry and the U.S. Food and Drug Administration (FDA) is the production and sale of chiral drugs . 

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