Hair Analysis for Drugs of Abuse XII. Determination of PCP and Its Major Metabolites, PCHP and PPC, in Rat Hair after Administration of PCP

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Abstract
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,Obis(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 be detected simultaneously.

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