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The therapeutic use of "antisense oligonucleotides" is a new approach to rational drug design (1). Antisense oligonucleotides are short, single-stranded oligonucleotides, which will bind to a complementary sequence of a cellular messenger RNA due to the high specificity of nucleic acid base pairing. Most of the antisense oligonucleotides, currently in drug development programs, are phosphorothioates. In drug development, both the purity of the active compound as well as possible metabolites need to be quantitatively analyzed and characterized (2,3). Capillary electrophoresis (CE) has proven to be a separation method with higher resolving power than traditional separation methods for oligonucleotides. [ABSTRACT FROM AUTHOR]