Editorial

The absence of appropriate elements of symmetry in molecules generatesconfigurations with specific properties which may be reflected as differences inthe pharmacodynamics and pharmacokinetics of the individual isomers. Thepoints of attention arising out of configurational isomerism include the need forenantiospecific analytical methods and study of increased complexity ofmetabolic, pharmacological and clinical aspects followed by regulatory meas-ures. In vivo racemization of thalidomide was overlooked, hence the 1969thalidomide tragedy. Since then world-wide attention has increasingly been givenin this direction. More and more drugs and candidate compounds are beingstudied for their configurational stability particularly on pharmaceutical andpharmacological time scales.

From the present day examples, profens constitute the largest single group ofnon-steroidal anti-inflammatory drugs and it has been indicated that the R-isomerof ibuprofen or ketoprofen may accumulate in fatty tissues; according to the 1991estimate the world market for anti-arthritis drugs was considered to be about$5000m. There is a welcome announcement from certain pharmaceutical giantsthat they are going to produce and market the single isomer of certain profensoffering an improved product with lower dose and reduced side effects. The US–FDA policy statement made in May 1992 is a significant step forward in thatcompanies will be required to submit data showing that the isomeric mixture issafe by conducting key biological tests on the individual enantiomers, though itwill continue to approve racemates on a case to case basis. A similar policy isawaited from EC-countries.

Chromatography, as an analytical method, since its conception by MichaelTswett in 1906 and its birth as a modern technique in 1943, has developed andexpanded through paper-, thin layer-, column-, gas- and gel-permeation-chromatography, and with its application, many new areas of industry andacademia, using microparticulate silica in HPLC and open tubular columns inGLC, it has reached a considerably mature and stable state. Recently, analyticalthin layer chromatography and supercritical fluid chromatography have attractedattention. New, unified nomenclature for chromatography has also been outlinedand issued by IUPAC, this took ten years to prepare with extensive discussionsby scores of chromatographers active in various fields of science and in differentgeographical areas (Ettre, 1994).

Probably the time has come when the term Chiral Chromatography may alsobe recognised as covering chromatographic separations of chiral compounds.

Chiral separations constitute a fast growing area of interest not only forchromatographers, particularly those working in pharmaceutical, agricultural andfine chemical industries, but also for the analytical chemists and chemistsworking on enantioselective synthesis. Many laboratories maintain large librariesof columns to fine tune each analysis. Several companies dealing with sales ofchemical reagents/equipment and accessories around the world have focusedtheir attention on bringing out different guide books and maintaining chiralseparation service laboratories to help prospective customers choose propercolumns and separation conditions, with endorsement of the customer’s ownsecrecy agreement. These guides summarize a large number of analysesperformed in various laboratories around the world. Choosing a proper columnis ultimately an empirical process and different workers will use differentstrategies.

Various CSPs have been designed for HPLC using different optically active p-acids and p-bases wherein resolution is achieved through a variety of interactionsincluding charge transfer, steric hinderance, dipole–dipole stacking, p-inter-actions and H-bonding, depending upon the configuration of the solute, providingformation of some sort of diastereomers. Most of the available CSPs are veryexpensive and chiral separations are known to be highly specific with respect toany given CSP. Thus CSPs with high efficiency and robustness, capable ofquantitative work continuously for a long time without any perceptibledegradation in performance and which in addition leave proven utility inresolving enantiomers of pharmaceutical compounds of widely differentchemical structure and biological activity such as cardiovascular, anti-inflamma-

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BIOMEDICAL CHROMATOGRAPHY, VOL. 11, 257–258 (1997)

tory/analgesic, adrenergic, antihistaminic, antimalarial, anaesthetic and otherdrugs are the need of the hour.

Concurrent with the development of synthetic methods leading to highenantioselectivity or to the desired pure enantiomer, quantitative commercialmethods are required to separate/resolve the enantiomeric/racemic mixtureswhile the biological data on the individual isomers with regards to Absorption,Distribution, Metabolism and Excretion studies is highly desirable to aid thedevelopment of superior therapeutics.

Ravi BhushanGuest Editor

REFERENCES

ETTRE, L. S. (1994). Chromatographic 38, 521. Biomed. Chromatogr. 11, in press(1997).

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© 1997 by John Wiley & Sons, Ltd. BIOMEDICAL CHROMATOGRAPHY, VOL. 11, 257–258 (1997)