piperidines and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine

We evaluated the usefulness of hair root analysis to diagnose acute phencyclidine (PCP) poisoning. Male rats were i.p. administered acute poisonous doses (80, 100 and 120 mg/kg) of PCP hydrochloride and the hair roots were plucked out with hair nippers at certain times after administration. The hair root samples were extracted with methanol/HCl. After evaporation of the solvent, the residue was derivatized with N,O-bis(trimethylsilyl) acetamide and analyzed with GC/MS. PCP was detected at high concentrations (up to 181.7 ng/mg) from all samples. The peak concentrations at every dose were observed at 6 h. The concentrations of PCP in the rat hair roots increased dose-dependently in the range of the doses. 1-(1-Phenylcyclohexyl)-4-hydroxypiperidine (PCHP) and trans-1-phenyl-1(4'-hydroxypiperidino)-4-cyclohexanol (t-PCPdiol) were also detected from 5 and 15 min to 48 h after administration, respectively. It is concluded that hair root is a useful specimen for the diagnosis of acute PCP poisoning because PCP, PCHP and t-PCPdiol are detected very soon after administration and a large amount of them is retained in hair root for a long time. PCHP was found from the early stage in hair roots and its concentration was higher than that of t-PCPdiol for 6 h. However, the concentration of t-PCPdiol became higher than that of PCHP after 6 h. These phenomena could be explained by the time lag of production of the primary (PCHP) and the secondary metabolite (PCPdiol).

Topics: Acute Disease; Animals; Biotransformation; Calibration; Gas Chromatography-Mass Spectrometry; Hair; Hallucinogens; Male; Phencyclidine; Piperidines; Rats

The paper reports the simultaneous detection hair of phencyclidine (PCP) and its two major metabolites, 1-(1-phenylcyclohexyl)-4-hydroxypiperidine (PCHP) and trans-1-(1-phenyl-4-hydroxycyclohexyl)-4'-hydroxypiperidine (t-PCPdiol) in human hair. The detection of these metabolites provides definitive evidence that a positive hair analysis result is due to active PCP use and not due to external contamination of the hair specimen. Hair (5 mg) from known PCP users was washed three times with 0.1% sodium dodecyl sulfate for 1 min before analysis. Three extraction methods were compared: methanol-5N HCl (20:1) (Method A), 10% HCl (Method B), and 2N sodium hydroxide digestion (Method C). PCP-d5 and PCHP-d5 were used as internal standards. Extracts were purified by Bond Elut Certify solid-phase extraction procedures. Samples were derivatized with N,O-bis-trimethylsilyl acetamide and analyzed by gas chromatography-mass spectrometry. Compared with Method A, the extraction efficiencies of Methods B and C for PCP were 83-89%; however, the extraction efficiencies of Methods B and C for the two metabolites were only half or less than that of Method A. Method A was therefore selected for the analysis of clinical hair specimens from eight PCP users. The coefficients of variation of this method (n = 5) for PCP at 4 ng/mg and for PCHP and t-PCPdiol at 0.2 ng/mg were 2.13, 6.09, and 9.38%, respectively. In the eight hair specimens, PCP values ranged between 0.33 and 14 ng/mg. PCHP between 0.02 and 0.12 ng/mg, and trans-PCPdiol between 0.09 and 0.45 ng/mg. It was found that t-PCPdiol was the major metabolite in the PCP users' hair specimens, although t-PCPdiol was a minor metabolite in the hair specimens of rats intoxicated with PCP.

Topics: Animals; Female; Hair; Humans; Illicit Drugs; Phencyclidine; Phencyclidine Abuse; Piperidines; Rats