[Show abstract][Hide abstract] ABSTRACT: A procedure that involves a high-performance liquid chromatographic system with silica-bonded columns and reversed-phase eluents was fitted from a previously described method to measure clozapine and desmethylclozapine plasma levels. Clozapine and its demethylated metabolite were extracted from alkalinized serum by a liquid-liquid extraction, separated in 10 min, then quantitated at 254 nm at a minimum concentration of 20 ng/mL. The standard curves were linear over the range of 50-3000 ng/mL (r > 0.99) both for clozapine and desmethylclozapine and the assay had good sensitivity and recovery. Intra- and interday coefficients of variation for 200 and 800 ng/mL controls were less than 11.5% for clozapine and desmethylclozapine. This simple and efficient assay was used to monitor clozapine and desmethylclozapine levels from some treatment-refractory schizophrenic patients.