title: Racemization and degradation of thioridazine and thioridazine 2-sulfone in human plasma and aqueous solutions.
abstract: We present two methods for the enantioselective analysis of thioridazine (THD) and thioridazine 2-sulfone (THD 2-SO(2)) in human plasma based on liquid-liquid extraction with diethyl ether and chiral resolution of the enantiomers on Chiralpak AD and Chiralcel OD-H columns, respectively. After validation, the methods were used to study the degradation and racemization of both drug and metabolite. Our results showed that both enantiomers of THD and THD 2-SO(2) were stable at varying temperatures, pH, and ionic strengths; however, solubility problems for THD and THD 2-SO(2) enantiomers were observed, mainly at pH 8.5. The influence of light on the stability of the THD and THD 2-SO(2) enantiomers was also studied. Degradation of the THD enantiomers was observed under UV light (254 and 366 nm) while THD 2-SO(2) enantiomers were stable at these wavelengths and also when exposed to visible light.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Masetto de Gaitani
authors.forename: Alexandre Souto
authors.initials: AS
authors.lastname: Martinez
authors.forename: Pierina Sueli
authors.initials: PS
authors.lastname: Bonato
mesh_terms: D014150:Antipsychotic Agents / Q000097:blood / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D012996:Solutions; D013237:Stereoisomerism; D013881:Thioridazine / Q000031:analogs & derivatives* / Q000097:blood* / Q000737:chemistry*
chemical_list: D014150:Antipsychotic Agents; D012996:Solutions; C476405:thioridazine 2-sulfone; D013881:Thioridazine