ANALYTICAL CHALLENGES IN CHEMICAL-ENZYMATIC DRUG TARGETING

The development of new methods of chemical enzymatic drug targeting (c hemical delivery systems and soft drugs) relies on specific and sensit ive analytical techniques. High-performance liquid chromatography has been a powerful technique that can separate complex mixtures of chemic al species involved in the enzymatic and/or chemical transformation in vivo and in vitro to produce the targeted drug. The successful chemic al separation requires specificity of interaction of the chromatograph ic column and the solute to resolve compounds with characteristic (som etimes subtle) chemical differences. Differing lipophilicity and the i onic or neutral nature of the species are the primary factors to be co nsidered during method development. Improving the specificity toward t he analyte has often been necessary to provide adequate detection limi ts for tissue samples derived from the site of action. Chromatography lacks, however, the power of identifying unknown species. Mass spectro metry, both coupled with chromatography and as a technique providing d irect specificity, may represent a viable solution. These issues, incl uding future perspectives, are discussed in this review.