TY - JOUR

T1 - 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

AU - Davidsen, Anders Bork

AU - Mardal, Marie

AU - Johansen, Sys Stybe

AU - Dalsgaard, Petur Weihe

AU - Linnet, Kristian

N1 - This article is protected by copyright. All rights reserved.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1002/dta.2807

DO - 10.1002/dta.2807

M3 - Journal article

C2 - 32311838

VL - 12

SP - 987

EP - 993

JO - Drug Testing and Analysis

JF - Drug Testing and Analysis

SN - 1942-7603

IS - 7

ER -