Determination of thioridazine enantiomers in human serum by sequential achiral and chiral high-performance liquid...

Quantitation of thioridazine (TRZ) enantiomers, (+)-TRZ and (-)-TRZ, in patient serums was performed by a sequential achiral and chiral HPLC method. The lower limit of quantitation was 50 ng/mL for each enantiomer, and the method was linear up to 1000 ng/mL. The within-run and between-run precision at 125 and 500 ng/mL of each enantiomer yielded coefficients of variation (CV) of less than 10% and less than 12%, respectively. Absolute recovery of 250 ng/mL racemic TRZ added to serum (n = 9) yielded mean recoveries of 77.2% and 77.8% for (+)-TRZ and (-)-TRZ, respectively. Absolute recovery of 1000 ng/mL racemic TRZ added to serum (n = 9) yielded mean recoveries of 74.0% and 74.7% for (+)-TRZ and (-)-TRZ, respectively. Significantly different TRZ enantiomer concentrations were present in patient serums. The mean serum concentration was 110 ng/mL for (+)-TRZ (n = 18), and 317 ng/mL for (-)-TRZ (n = 21). The ratios of (-)-TRZ to (+)-TRZ ranged from 2.2 to 5.3, with a mean of 3.3. Variations in the concentration of TRZ enantiomers may contribute to the lack of correlation between serum TRZ values and therapeutic effect.