Etude des paramètres physico-chimiques impliqués dans les séparations énantiosélectives de xénobiotiques chiraux : applications en toxicologie clinique et médico-légale

Abstract : The amphetamine-type stimulants (ATS) and methadone (MTD) are chiral drugs of abuse, whose enantiomers present different pharmacological properties. Thus, the determination of the R/S ratios of these analytes could be helpful for the interpretation of toxicological results in clinical and forensic cases. The enantiomers of ATS extracted from the hair matrix have been quantified by gas chromatography-mass spectrometry using a new chiral derivatization agent, (2S,4R)-N-heptafluorobutyryl-(4-heptafluorobutoyloxy)-prolyl chloride. The method showed excellent limits of detection compared to former studies. This study permitted us to determine the enantiomeric ratios of the ATS in hair. The results pointed out that the incorporation mechanism of ATS into hair matrix seems not to be enantioselective. Furthermore, the R/S ratios remained relatively stable along hair shafts. The enantioselective quantification of methadone and its primary metabolite EDDP in oral fluid was studied using capillary electrophoresis (CE). Separations were obtained using highly sulphated ?-cyclodextrins as chiral selectors. A predominance of (R)-MTD and (S)-EDDP were observed in oral fluid. Finally, computational simulations showed that molecular modelling is an additional tool for the prevision of the migration order of enantiomers such as ATS, MTD or EDDP separated by CE using cyclodextrins as chiral selectors.
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Liliane Martins Ferreira. Etude des paramètres physico-chimiques impliqués dans les séparations énantiosélectives de xénobiotiques chiraux : applications en toxicologie clinique et médico-légale. Autre. Université Henri Poincaré - Nancy 1, 2007. Français. ⟨NNT : 2007NAN10056⟩. ⟨tel-01748246⟩

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