Trace analysis of haloperidol and its chiral metabolite in plasma by capillary electrophoresis

Capillary zone electrophoresis was developed for the simultaneous determination of haloperidol (HP) and its chiral metabolites [(+)- and (-)- reduced haloperidol, (+)- and (-)-RHP] in human plasma. The method involved the presence of an internal standard and liquid-liquid extraction from plasma. After concentration, the residue from the organic extract was dissolved in aqueous acid for capillary electrophoretic analysis. The background electrolyte was Tris-phosphate buffer with dimethyl-beta-cyclodextrin and PEG 6000. In spiked plasma the quantitative ranges were 40-400 nM for HP and 50-500 nM for (+)-RHP or (-)-RHP. The intra-day and inter-day relative standard deviations (n = 3) were all < 20% for each substance. The detection limits were found to be 15 ng/ml for HP and 30 ng/ml for both enantiomers of RHP (S/N = 3, injection 20 s). All recoveries were > 70%. We investigated the in vivo metabolism of HP in Chinese schizophrenia patients. The results show that (-)-RHP seems to be the only chiral metabolite from these two HP-dosed patients.