In vitro and in vivo metabolism and detection of 3-HO-PCP, a synthetic phencyclidine, in human samples and pooled human hepatocytes using high resolution mass spectrometry.

The phencyclidine (PCP) analogue 3-HO-PCP, a potent dissociative new psychoactive substance, was detected in a law enforcement seizure and forensic samples in Denmark. Its toxicokinetic properties were investigated for the first time. The unbound fraction in plasma was 0.72 ± 0.09. Four in vitro metabolites were identified after incubation with human hepatocytes; in vivo, the O-sulphate-conjugated metabolite was not detected, and the N-dealkylated-COOH metabolite was the main metabolite in deconjugated urine. In blood and brain, 3-HO-PCP and its O-glucuronidated metabolite were the primary analytical targets. Drug levels in blood were 0.013 mg/kg in a living subject and 0.095 mg/kg in a deceased subject. Post-mortem brain concentration was 0.16 mg/kg, 1.5-fold higher than in post-mortem blood.

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Abstract

The new psychoactive substance (NPS) 3-HO-PCP, a phencyclidine (PCP) analogue, was detected in a law enforcement seizure and in forensic samples in Denmark. Compared to PCP, 3-HO-PCP is known to be a more potent dissociative NPS, but no toxicokinetic investigations of 3-HO-PCP are yet available. Therefore, 3-HO-PCP was quantified in in vivo samples, and the following were investigated: plasma protein binding, in vitro and in vivo metabolites and metabolic targets. All samples were separated by liquid chromatography and analysed by mass spectrometry. The unbound fraction in plasma was determined as 0.72 ± 0.09. After in vitro incubation with pooled human hepatocytes, four metabolites were identified: a piperidine-hydroxyl-and piperidine ring opened N-dealkyl-COOH metabolite, and O-glucuronidated- and O-sulphate-conjugated metabolites. In vivo, depending on sample and sample preparation, fewer metabolites were detected as the O-sulphate-conjugated metabolite was not detected. The N-dealkylated-COOH metabolite was the main metabolite in the deconjugated urine sample. In vivo analytical targets in blood and brain samples were 3-HO-PCP and the O-glucuronidated metabolite, with 3-HO-PCP having the highest relative signal intensity. The drug levels of 3-HO-PCP quantified in blood were 0.013 and 0.095 mg/kg in a living and a deceased subject, respectively. 3-HO-PCP concentrations in deconjugated urine in a sample from a living subject and in post-mortem brain were 7.8 and 0.16 mg/kg, respectively. The post mortem results showed a 1.5-fold higher concentration of 3-HO-PCP in the brain tissue than in the post mortem blood sample.