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Racemization and degradation of thioridazine and thioridazine 2‐sulfone in human plasma and aqueous solutions
Author(s) -
Masetto de Gaitani Cristiane,
Martinez Alexandre Souto,
Bonato Pierina Sueli
Publication year - 2003
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.10240
Subject(s) - chemistry , thioridazine , racemization , degradation (telecommunications) , aqueous solution , sulfone , organic chemistry , pharmacology , medicine , chlorpromazine , telecommunications , computer science
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. Chirality 15:479–485, 2003. © 2003 Wiley‐Liss, Inc.