Determination of the enantiomers of thioridazine, thioridazine 2-sulfone, and of the isomeric pairs of thioridazine 2-sulfoxide and thioridazine 5-sulfoxide in human plasma.

Détails

ID Serval
serval:BIB_CA4F40BC646A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Determination of the enantiomers of thioridazine, thioridazine 2-sulfone, and of the isomeric pairs of thioridazine 2-sulfoxide and thioridazine 5-sulfoxide in human plasma.
Périodique
Journal of Chromatography. B, Biomedical Applications
Auteur(s)
Eap C.B., Koeb L., Powell K., Baumann P.
ISSN
1572-6495 (Print)
ISSN-L
1572-6495
Statut éditorial
Publié
Date de publication
1995
Peer-reviewed
Oui
Volume
669
Numéro
2
Pages
271-279
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Thioridazine is a commonly prescribed phenothiazine drug administered as a racemate and it is believed that its antipsychotic effect is mainly associated with (R)-thioridazine. A method based on high-performance liquid chromatography has been developed for the determination of the enantiomers of thioridazine and thioridazine 2-sulfone (THD 2-SO2 or sulforidazine) and of the enantiomers of the diastereoisomeric pairs of thioridazine 2-sulfoxide (THD 2-SO or mesoridazine) and thioridazine 5-sulfoxide (THD 5-SO) in the plasma of thioridazine-treated patients. The method involves sequential achiral and chiral HPLC. The limits of quantitation for total (R) + (S) concentrations were found to be 15 ng/ml for thioridazine and 5 ng/ml for its metabolites. The limits for the determination of the (R)/(S) ratios were found to be 60 ng/ml for racemic THD and 10 ng/ml for racemic THD 2-SO, THD 2-SO2, THD 5-SO (FE) and THD 5-SO (SE). The method has been used to determine the concentrations of the enantiomers of thioridazine and of its metabolites in the plasma of a patient treated with 100 mg of racemic thioridazine hydrochloride per os per day for 14 days. The results show a high enantioselectivity in the metabolism of this drug: the (R)/(S) ratios for THD, THD 2-SO (FE), THD 2-SO (SE), THD 2-SO2, THD 5-SO (FE) and THD 5-SO (SE) were found to be 3.90, 1.22, 6.10, 4.10, 0.09 and 28.0, respectively.
Mots-clé
Antipsychotic Agents/blood, Chromatography, High Pressure Liquid, Humans, Isomerism, Spectrometry, Fluorescence, Stereoisomerism, Thioridazine/analogs & derivatives, Thioridazine/blood
Pubmed
Web of science
Création de la notice
01/03/2013 11:31
Dernière modification de la notice
20/08/2019 16:45
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