ENANTIOMERIC DERIVATIZATION FOR BIOMEDICAL CHROMATOGRAPHY

Derivatization reactions aimed at creating the basis for the chromatographic resolution of biologically and pharmaceutically important enantiomers are reviewed, with emphasis on the literature published in the last 10 years. Three main aspects of chiral derivatization are discussed. (a) Enantiomers containing suitable functional groups (amino, carboxyl, hydroxyl, epoxy, etc.) are transformed into covalently bonded diastereomeric derivatives using homochiral derivatizing agents. The diastereomers formed (esters, amides, urethanes, urea and thiourea, etc., derivatives) can be separated on achiral stationary phases. The derivatization reactions often afford further advantages, such as the improvement of chromatographic properties and the detectability of the solutes using UV and fluorimetric detectors. (b) Covalent but achiral derivatization is often necessary even with the use of chiral stationary phases enabling in principle direct enantioseparations (Pirkle-type columns, cyclodextrin-bonded phases, glycoprotein column and functionalized cellulose columns). The main goals of these derivatization reactions (which are analogous to those discussed above), are to introduce functional groups into the molecule of the enantiomers that improve the possibilities for chiral interactions or block functional groups to avoid non-specific interactions. (c) In the broader sense, the dynamic formation of diastereomers using chiral mobile phase additives (cyclodextrins, various reagents to form diastereomeric ion pairs, adducts, mixed metal complexes) can also be considered to be chiral derivatization reactions and is therefore briefly discussed also.