An Improved Sensitive Assay for Simultaneous Determination of Plasma Haloperidol and Reduced Haloperidol Levels by Liquid Chromatography Using a Coulometric Detector

Abstract

A simple, highly sensitive and specific high-performance liquid chromatographic method that uses a coulometric detector for the simultaneous assay of haloperidol and reduced haloperidol in human plasma has been developed, using bromoperidol as the internal standard. A reversed phase C8 5-.mu.m column (25 .times. 0.46 cm) and a mobile phase of phosphate buffer (pH 7.0), acetonitrile, and methanol (40:20:40 vol/vol) are used for separating the analytes. The analytes are extracted from alkalinized plasma using a mixture of pentane and isopropanol (95:5 vol/vol) and purified by back extraction into a perchloric acid solution. Teflon tubes with screw caps are used throughout the extraction work. The compounds are oxidized at a potential of +0.90 V against a Ag/AgCl reference electrode. The detection limit of the assay is 50 ng/L using 1 mL of plasma. The average interassay coefficient of variation for samples of concentration 1-40 .mu.g L is .apprx. 8%. Possible drug interferences in the assay have been studied. The absolute recovery of the method is .apprx.80%. The assay has been validated by quantitating 150 schizophrenic patient''s samples.