Study on thioridazine 5-sulfoxide epimerization and degradation by capillary electrophoresis.
We present a method for the stereoselective analysis of thioridazine 5-sulfoxide (THD 5-SO) in human plasma based on liquid-liquid extraction with diethyl ether and chiral resolution of the stereoisomers by capillary electrophoresis using hydroxypropyl-beta-cyclodextrin and sulfated beta-cyclodextrin as chiral selectors. The method showed recovery rates of 85.5% for both THD 5-SO (slow-eluting, SE) enantiomers. The coefficients of variation observed in the precision studies, as well as the accuracy values, were below 10%. After validation, the method was used to study the stability and configurational changes of this THD metabolite. Our results showed that both enantiomers of THD 5-SO (SE) were stable under conditions of variation of temperatures (38 degrees C, 4 degrees C and -20 degrees C), pH (5.0, 7.0 and 8.5) and ionic strengths (0.2, 0.5 and 1.0 mol/L). The influence of light on the stability of the THD 5-SO (SE) stereoisomers was also studied using standard solutions prepared in methanol and an inversion in configuration was observed under UV light (254 and 366 nm).
Masetto de Gaitani
Cristiane
C
Faculdade de Ciências Farmacêuticas de Ribeirao Preto-USP, Ribeirao Preto-USP, 14040-903 Brazil.
Martinez
Alexandre Souto
AS
Bonato
Pierina Sueli
PS
D003505:Cyclodextrins; D004355:Drug Stability; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D009994:Osmolar Concentration; D013237:Stereoisomerism; D013696:Temperature; D013881:Thioridazine / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism*; D014466:Ultraviolet Rays
D003505:Cyclodextrins; C041140:thioridazine-5-sulfoxide; D013881:Thioridazine