A novel method for ketoprofen resolution using enzymes through a non-biotransformation route was reported. Racemic ketoprofen was dissolved in organic solvents containing ion-paired enzymes and the solvents were then partially evaporated leading to an enantioselective crystallization of the two enantiomers. An enantiomeric excess (e.e.) of 67% of S-ketoprofen in the remaining solutions was achieved by two-step crystallization from isooctane containing ion-paired Candida rugosa lipase or alpha-chymotrypsin. This enantioseparation was ascribed to the difference in dissociation of the enzyme-enantiomer complexes. (c) 2006 Elsevier B.V. All rights reserved.