DETERMINATION OF 4-(4-CHLOROPHENYL)-4-HYDROXYPIPERIDINE, A METABOLITEOF HALOPERIDOL, BY GAS-CHROMATOGRAPHY WITH ELECTRON-CAPTURE DETECTION

An electron-capture gas chromatographic procedure was developed for th e analysis of 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP), a metabol ite of haloperidol. The assay involved basic extraction of this metabo lite from the biological samples, followed by back-extraction with HCl . After basification of the acid phase, extractive derivatization with pentafluorobenzoyl chloride in toluene was conducted. The pentafluoro benzoyl derivative was quantified on a gas chromatograph equipped with a fused-silica capillary column, an electron-capture detector and a p rinter-integrator. N-(3-Trifluoromethylphenyl)piperazine was carried t hrough the procedure as an internal standard and calibration curves we re determined for each assay run. The procedure was demonstrated to be linear and reproducible and was utilized to detect and quantify CPHP in urine, plasma, brain and liver samples from rats treated with halop eridol. The structure of the derivatized metabolite was confirmed by g as chromatography-mass spectrometry.