Megabore capillary gas-liquid chromatographic method with nitrogen-phosphorus selective detection for the assay of haloperidol and reduced haloperidol in serum: results of therapeutic drug-monitoring during acute therapy of eight schizophrenics.

A gas chromatographic method using a HP-5 megabore capillary and nitrogen-phosphorus selective detection for the quantitative analysis of haloperidol (H) and reduced haloperidol (RH) in human serum or plasma is described. A 3-step liquid-liquid extraction is applied. The extraction yield of this procedure is 63% for haloperidol at 20 ng/ml. The limits of detection are 0.4 ng/ml for haloperidol and 1.0 ng/ml for the metabolite if 2 ml of body fluid are applied. At 10 ng/ml the within-day precision is 4.5% for H and 8.3% for RH. Serum levels of eight schizophrenic patients have been monitored weekly over a therapeutic period of six weeks. Seven patients mainly had metabolite ratios RH/H < 1 over the entire period of investigation. They exhibited a linear correlation between dose and serum concentration of haloperidol. In contrast, one patient had metabolite ratios RH/H > 1 over the entire period of the study. Due to considerable increased serum concentrations this patient did not show a linear correlation between the dose and the serum level of haloperidol.