Abstract
The fate of a dodecathymidine prodrug in cell extract was monitored by MALDI-TOF MS. This technique allows a facile identification and a relative quantification of metabolites produced. We showed that the relative peak intensities were similar to the relative metabolite proportions that permitted the determination of their half-lives. The oligonucleotide prodrug was fully metabolized to yield the T12 phosphorothioate likely through a carboxyesterase mediated mechanism.
ACKNOWLEDGMENTS
This work was supported by grants from “Association pour la Recherche contre le Cancer” (ARC) and the “Comités de l'Aude et des Pyrénées Orientales de la Ligue contre le Cancer”. JCB thanks the “ADER” for the award of a research studentship. We thanks Dr. A.-M. Aubertin for the gift of the cell extract.