Simultaneous determination of plasma haloperidol and its metabolite reduced haloperidol by liquid chromatography with electrochemical detection. Plasma levels in schizophrenic patients treated with oral or intramuscular depot haloperidol.

A simple and highly sensitive liquid chromatographic method with electrochemical detection for the simultaneous determination of haloperidol and its metabolite reduced haloperidol in human plasma has been developed. The sample preparation for the analysis involves a simple one-step extraction procedure with 10% methylene chloride in pentane. The compounds were separated on a cyano column maintained at a temperature of 40 degrees C and were detected electrochemically by a flow-through analytical cell kept at +0.95 V. The standard curve is linear over the range of 0.1 to 15 ng/ml and the lower limit of quantitation is 0.1 ng/ml for haloperidol and 0.25 ng/ml for reduced haloperidol which is equivalent to approximately 40 pg on column when 1 ml of plasma was used for the analysis. The lower limit of quantitation for reduced haloperidol can be extended to 0.1 ng/ml if 2 ml of plasma is used in the analysis. The coefficient of variation of the determination of plasma levels by this method over the standard curve concentration range was less than 10%. Commonly co-administered drugs and other neuroleptics used in conjunction with haloperidol did not interfere in the determination of either haloperidol or reduced haloperidol. This method has been successfully used for the determination of haloperidol and reduced haloperidol in plasma and their levels in patients treated with various doses oral haloperidol or intramuscular haloperidol decanoate are reported.