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2016 (v.24 no.3)

Translational and Clinical Pharmacology

Korean Society for Clinical Pharmacology and Therapeutics
ISSN: 2289-0882

  • Development and validation of a HPLC-UV method for 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP), a toxic metabolite of haloperidol, in humans: providing in vivo evidence of CYP3A4-mediated CPHP formation

    Ji-Young Park, Jae-Gook Shin

    TCP | v.24, no.3, pp.147-151, Sep, 2016


    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

    containing 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 recovered 

    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.


    Haloperidol, CPHP, CYP3A4, HPLC