Separation of antipsychotic drugs (clozapine, loxapine) and their metabolites by capillary zone electrophoresis.

Two antipsychotic drugs (clozapine and loxapine) and six metabolites, N-demethylclozapine, clozapine N-oxide, N-demethylloxapine (amoxapine), 7-hydroxyloxapine, 8-hydroxyloxapine, 8-hydroxyamoxapine, were separated by capillary zone electrophoresis. Variation of pH and ionic strength of the acidic phosphate buffer (pH below 4) did not enable the separation of loxapine and one of its metabolites. Resolution of the single parent drugs and their metabolites was possible in background electrolytes (phosphate, pH 3.5, 60 mmol/l) containing either 0.2% (w/v) polyvinylpyrrolidone as replaceable pseudo-stationary phase, or 0.75 mmol/l beta-cyclodextrin added as complex-forming agent. Full separation of the mixture with baseline resolution of all analytes was obtained with a background electrolyte with heptakis-6-sulfato-beta-cyclodextrin added as negatively charged complexation agent with improved separation selectivity.