Kinetics study of the biotransformation of an oligonucleotide prodrug in cells extract by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry

The fate of a dodecathymidine prodrug in cell extract was monitored by MALD I-TOF MS. This technique allows a facile identification and a relative quan tification of metabolites produced. We showed that the relative peak intens ities were similar to the relative metabolite proportions that permitted th e determination of their half-lives. We found a good fit between the calcul ated kinetics curves and the experimental points. The oligonucleotide prodr ug was fully metabolized to yield the dodecathymidine phosphorothioate Like ly through a carboxyesterase mediated mechanism. (C) 2001 Elsevier Science BN. Ail rights reserved.