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

Capillary zone electrophoresis was developed for the simultaneous determina tion of haloperidol (HP) and its chiral metabolites [(+)- and (-)- reduced haloperidol, (+)- and (-)-RHP] in human plasma. The method involved the pre sence of an internal standard and liquid-liquid extraction from plasma, aft er concentration, the residue from the organic extract was dissolved in aqu eous acid for capillary electrophoretic analysis. The background electrolyt e was Tris-phosphate buffer with dimethyl-beta-cyclodextrin and PEG 6000. I n 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 devi ations (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 me tabolism of HP in Chinese schizophrenia patients. The results show that (-) -RHP seems to be the only chiral metabolite from these two HP-dosed patient s. (C) 1999 Elsevier Science B.V. All rights reserved.