Hydroxy metabolites of phencyclidine. Identification and quantitation of two novel metabolites.

A new sensitive and specific GC-MS assay was developed to quantify monohydroxy metabolites of phencyclidine (PCP) from biological samples. The method is based on the two-step extraction of PCP and related basic metabolites in an organic solvent followed by a capillary column GC separation and mass selective detection of the extract derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide. The detection limit of the method is about 5 pmol with a linear standard curve to 3 nmol/injection. The assay was used for the quantification of monohydroxy metabolites in the urine of PCP-dosed mice and rats. A new compound (specifically selected for this study), 1-phenyl-1-(1-[3-hydroxymethyl]piperidinyl)cyclohexane, was used as the internal standard. The internal standard was selected to closely mimic the chemical characteristics of potential alicyclic hydroxy metabolites of PCP. The in vitro biotransformation of PCP by mouse and rat liver microsomes also was studied. The presence of a recently identified metabolite, 3-phenyl-3-(1-piperidinyl)-trans-cyclohexanol was confirmed. A new metabolite, 1-phenyl-1-(1-piperidinyl-3-ol)cyclohexane, was identified and quantified in the urine and liver microsomal preparations.