Development and validation of a HPLC-UV method for 4-(4-chlorophenyl)-4-hydroxypi- peridine (CPHP), a toxic metabolite of haloper- idol, in humans: providing in vivo evidence of CYP3A4-mediated CPHP formation

• Published in: Translational and clinical pharmacology pp. 147 - 151
• Main Authors: 박지영, 신재국
• Format: Journal Article
• Language: English
• Published: 대한임상약리학회 01.09.2016
• Subjects: 의약학
• ISSN: 2289-0882; 2383-5427

We developed a high-performance liquid chromatographic procedure for the determination of 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP), a toxic metabolite of haloperidol, in human. Chromatographic analysis was performed on a reverse-phase C18 column with a mobile phase con-taining 50 mM potassium phosphate buffer/acetonitrile (75:25, vol/vol) using UV detection with a wavelength of 220 nm. The limits of detection for CPHP were 1 ng/ml in urine and the assay was linear over the concentration range of 2-500 ng/ml for urine. This analytical method was applied to measure CPHP in human. Nineteen healthy subjects were enrolled and all subjects received a single oral dose of 5 mg haloperidol following a treatment of placebo or itraconazole at 200 mg/day for 10 days in a randomized crossover manner. CPHP was detected in urine samples and average recov¬ered amount of CPHP was 81.31 μg/24 hr in the placebo phase and it was significantly reduced to 30.34 μg/24 hr after itraconazole treatment. The finding provides in vivo evidence that CPHP is an in vivo metabolite of haloperidol in human and its formation is mediated by CYP3A4. KCI Citation Count: 0