Chiral non-steroidal anti-inflammatory drugs-a review

Chromatographic behaviors for enantiomeric separation of arylpropionic acid drugs were systematically developed by reversed phase-high performance liquid chromatography (RP-HPLC) using cellulose-tris-(4-methylbenzoate) (CTMB) as chiral stationary phase (CSP). The effects of the composition of the mobile phase, additives and temperature on chiral separation of flurbiprofen, pranoprofen, naproxen, ibuprofen and loxoprofen were further investigated. The enantiomers had been successfully separated on CSP of CTMB by the mobile phase of methanol-% (v/v) formic acid except naproxen by acetonitrile-% (v/v) formic acid at 25 °C. The mechanisms of the racemic resolution for the above mentioned five drugs are discussed thermodynamically and structurally. The resolutions between respective enantiomers for arylpropionic acid drugs on CTMB had significant differences due to their chromatographic behaviors. The order of resolutions ranked pranoprofen, loxoprofen, flurbiprofen, ibuprofen and naproxen. The method established has been successfully applied to the determination of the enantiomers of the five drugs in commercial preparations under the optimized conditions. It proved that the method is simple, reliable and accurate.

Eur J Clin Pharmacol (1992) 42:23%256 EuropeanJourna,of (~[]~l~(~Q~ @ Springer-Verlag 1992 F>BQ[ssQCerleg ] Special article Enantioselective pharmacodynamics and pharmacokinetics of chiral non-steroidal anti-inflammatory drugs A. M. Evans* Department of Pharmacy, University of Manchester, Manchester, UK Received: March 1,1991/Accepted in revised form: June 24, 199I Key words: Non-steroidal anti-inflammatory drugs, En- antioselective; Enantiomers; pharmacodynamics, pharmacokinetics, stereoselective The non-steroidal anti-inflammatory drugs (NSAIDs) encompass a variety of structural classes, including salicylates, pyrazoles, oxicams, fenamates, arylacetic acids, and arylpropionic acids. Despite this structural diversity, there is an important feature which distinguishes a sub-class of NSAIDs from a!l others - chirality. A number of NSAIDs contain a chiral carbon atom (a tetrahedral carbon atom covalently bonded to four different substituents) and therefore exist as two non-superimposable mirror-image forms or enantiomers (Table 1). Most of these chiral agents are arylalkanoic acids, in which the chiral carbon atom is adjacent to a carboxylic acid functional group. During the early screening and testing of some of the older chiral arylalkanoic acids, medicinal chemists became aware that molecular stereochemistry played an important role in determining anti-inflammatory activity. It was commonly reported, for example, that anti-inflammatory activity was elicited by one enantiomer only [Fried et al. 1973; Harrison

Chiral non-steroidal anti-inflammatory drugs-a review

chiral non-steroidal anti-inflammatory drugs-a review


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