Nucleoside analogues comprise an important class of current and potential anticancer and antiviral drugs.These agents usually require activation by intracellular phosphorylation and often affect either DNA or RNA synthesis.The ability to measure and characterize the active phosphorylated metabolites of these compounds, which may be formed at only trace levels, as well as assess their effect on endogenous intracellular nucleotide pools, is therefore critical for new drug development and for subsequent therapeutic evaluation.Capillary electrophoresis (CE) offers an attractive alternative to HPLC-based methods for nucleotide analysis because of its simplicity, high separating power and charge-based separation mechanism.Its use for trace nucleotide analysis, however, has been limited by its poor concentration limit of detection due to the very small volumes usually required for sample loading.