title: Kinetics study of the biotransformation of an oligonucleotide prodrug in cells extract by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry.
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. We found a good fit between the calculated kinetics curves and the experimental points. The oligonucleotide prodrug was fully metabolized to yield the dodecathymidine phosphorothioate likely through a carboxyesterase mediated mechanism.
authors: Laboratoire de Chimie Organique Biomoléculaire de Synthèse, UMR 5625 CNRS-UM II, Université Montpellier II, France.
authors: J C
authors: JC
authors: Brès
authors: F
authors: F
authors: Morvan
authors: I
authors: I
authors: Lefebvre
authors: J J
authors: JJ
authors: Vasseur
authors: A
authors: A
authors: Pompon
authors: J L
authors: JL
authors: Imbach
mesh_terms: D001711:Biotransformation; D002457:Cell Extracts; D009841:Oligonucleotides / Q000737:chemistry / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000493:pharmacokinetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013936:Thymidine / Q000737:chemistry
chemical_list: D002457:Cell Extracts; D009841:Oligonucleotides; D011355:Prodrugs; D013936:Thymidine