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
DRUG TESTING AND ANALYSIS
Authors: Davidsen, Anders Bork; Mardal, Marie; Johansen, Sys Stybe; Dalsgaard, Petur Weihe; Linnet, Kristian
Abstract
The new psychoactive substance (NPS) 3-HO-PCP, a phencyclidine (PCP) analog, was detected in a law enforcement seizure and in forensic samples in Denmark. Compared with 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 analyzed 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-sulfate-conjugated metabolites. In vivo, depending on the sample and sample preparation, fewer metabolites were detected, as the O-sulfate-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. The 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.
Cannabis Use Is Associated with Increased Mechanical Ventilation and Polysubstance Use in Trauma Patients
AMERICAN SURGEON
Authors: Banks, Kian; Biswas, Subarna; Wong, Monica; Byerly, Saskya; Clark, Damon; Lam, Lydia; Inaba, Kenji; Demetriades, Demetrios
Abstract
Recent policy changes in California regarding cannabis use underscore the need to study outcomes and prevalence of this drug in trauma. Our study aims to study the prevalence of cannabis use and associations with injury types and outcomes in Los Angeles County trauma patients. Data were reviewed from 21,276 adult patients from a Los Angeles countywide database spanning five years (2012-2016), who underwent urine toxicology testing in the ED after sustaining a traumatic injury. The percentage of trauma patients using marijuana increased from 36 to 43 per cent over the five-year period. On univariate analysis, cannabis-positive patients were significantly younger and more likely male, with lower median systolic blood pressure and heart rate on arrival in the ED. A higher proportion of cannabis users had penetrating trauma, and 48 per cent of cannabis users also tested positive for amphetamines, cocaine, opioids, or Phencyclidine. On multivariate analysis, cannabis was associated with an increase in need for mechanical ventilation after adjusting for age, admission Glasgow Coma Score, gender, polysubstance use, blunt or penetrating mechanism, and Injury Severity Score, and was not associated with increases in mortality or ICU length of stay.