Racemization and degradation of thioridazine and thioridazine 2-sulfone in human plasma and aqueous solutions

We present two methods for the enantioselective analysis of thioridazine (THD) and thioridazine 2‐sulfone (THD 2‐SO2) 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‐SO2 were stable at varying temperatures, pH, and ionic strengths; however, solubility problems for THD and THD 2‐SO2 enantiomers were observed, mainly at pH 8.5. The influence of light on the stability of the THD and THD 2‐SO2 enantiomers was also studied. Degradation of the THD enantiomers was observed under UV light (254 and 366 nm) while THD 2‐SO2 enantiomers were stable at these wavelengths and also when exposed to visible light. Chirality 15:479–485, 2003. © 2003 Wiley‐Liss, Inc.