Hair analysis for drugs of abuse .12. Determination of PCP and its major metabolites, PCHP and PPC, in rat hair after administration of PCP

We developed an analytical method for the simultaneous detection of phencyclidine (PCP) and its metabolites, 4-phenyl-4-piperidinocyclohexanol (PPC)and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine (PCHP), in rat hair. Three pigmented, hairy rats were intraperitoneally administered PCP hydrochloride (HCl) at 0.05-0.5 mg/kg once a day for 10 successive days. Animal hair was shaved just before the first administration, and the newly grown hair was collected 4 weeks after the first administration. After the rat hair sample was washed three times with 0.1% sodium dodecyl sulfonate and water, separately, and dried in a desiccator, 20 mg of finely cut hair was extracted with 2 mL methanol-5N HCl (20:1) under ultrasonication for 1 h, followed by storage at room temperature for 14 h. Following filtration and evaporation of the extract, it was purified with Bond Elut Certify® in the usual manner, and the extract was derivatized with N,O-bis(trimethylsilyl) acetamide for gas chromatographic-mass spectrometric analysis using deuterated PCP, PPC, and PCHP as internal standards. The selected ions were monitored at m/z 186, 200, and 242 for PCP, m/z 172, 288, and 331 for trimethylsilyl (TMS) PCHP, and m/z 200, 254, and 331 for TMS PPC. PCP, PCHP, and PPC were simultaneously detected in the rat hair down to 0.1 mg/kg PCP HCl. Even at the dose of 0.05 mg/kg, PCP was clearly detected in the rat hair. Based on the area under the concentration versus time curve (AUC) in plasma (1460 ng · min/mL), the PCP concentration (3.34 ng/mg) in the rat hair was quite high. The incorporation rates into hair (concentration in hair/AUC) of PCP, PCHP, and trans-PPC were 2.29, 1.65, and 0.50, respectively, at 0.5 mg/kg. Our results suggest that hair could be a useful specimen for confirmation of active past PCP use because PCP and its metabolites can he detected simultaneously.