Determination of thioridazine enantiomers in human serum by sequential achiral and chiral high-performance liquid chromatography.
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.
Jortani
S A
SA
Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0597.
Poklis
A
A
D002851:Chromatography, High Pressure Liquid; D006801:Humans; D016014:Linear Models; D015203:Reproducibility of Results; D013237:Stereoisomerism; D013881:Thioridazine / Q000097:blood*
D013881:Thioridazine