Liquid Chromatographic Determination of Reduced Haloperidol and Haloperidol Concentrations in Packed Red Blood Cells from Humans*

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Abstract
Haloperidol (H) is a neuroleptic drug that has one known biologically active metabolite, reduced haloperidol (RH). A liquid chromatographic method is described for the determination of both compounds in human red blood cell (RBC) samples. The drugs were extracted into hexane at high pH and back-extracted into 0.1M HCI. The acid solution was then analyzed by reversed-phase chromatography under the following conditions: column was ultrasphere ODS; eluant was acetonitrile:0.085M phoehate buffer (30:70), final pH was 3.5, flow rate was 2 mL/min; detection was by light absorption at 246 nm for H and 220 nm for RH. The minimum limits of quantitation for H and RH were 0.25 and 0.1 ng/mL of packed RBC respectively. For six selected patients on 10 or 20 mg per day of oral haloperidol the RBC to plasma concentration ratios for RH and H were 2.20 ± 0.9 (SD) and 0.81 ± 0.26, respectively. The data indicate that RH is more concentrated in RBC than in plasma.