Racemization and Degradation of Thioridazine and Thioridazine 2-Sulfone in Human Plasma and Aqueous Solutions

摘要

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.