Biol. Pharm. Bull. 29(12) 2479—2482 (2006)

Haloperidol (HAL, Fig. 1) has been used extensively as a neuroleptic for more than 40 years, and acts mainly as a blocker of dopamine D1 or D2 receptors. The metabolites of HAL include a reduced form, 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP, Fig. 1) and others. Structurally, CPHP resembles 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which induces severe neurotoxicity, including Parkinson-like disease and dyskinesia. Ablordeppey et al. reported that CPHP induces a delayed and persistent freezing of movement. This action may involve sigma receptors, but not the dopamine D2 receptor. Bromperidol (BRO, Fig. 1) is also used in the treatment of patients with psychiatric disease and is a close structural analogue of HAL. The metabolic fate of BRO is similar to that of HAL. Acute dystonia is a side effect of BRO treatment. 4-(4-Bromophenyl)-4-hydroxypiperidine (BPHP, Fig. 1) produced by N-dealkylation of BRO may be partly responsible for the disorders induced by BRO treatment. There is currently no information about the determination or pharmacokinetics of BPHP. Recently, we determined CPHP levels in biological fluids from rats by HPLC with fluorescence detection after pre-column derivatization using 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), and the method was applied to study the disposition kinetics of CPHP after HAL administration in rats. In addition, BPHP determination in phosphateSensitive Determination of 4-(4-Bromophenyl)-4-hydroxypiperidine, a Metabolite of Bromperidol, in Rat Plasma by HPLC with Fluorescence Detection after Pre-column Derivatization Using 4-Fluoro-7-nitro-2,1,3-benzoxadiazole