Phase I Metabolism of Synthetic Cannabinoid Receptor Agonist PX-1 (5F-APP-PICA) via Incubation with Human Liver Microsomes and UHPLC-HRMS.

  title={Phase I Metabolism of Synthetic Cannabinoid Receptor Agonist PX-1 (5F-APP-PICA) via Incubation with Human Liver Microsomes and UHPLC-HRMS.},
  author={Brandon C Presley and Barry K Logan and Susan A. Jansen-Varnum},
  journal={Biomedical chromatography : BMC},
Studies of the metabolic and pharmacological profiles of indole carboxamide synthetic cannabinoids (a prevalent class of New Psychoactive Substances) are critical in ensuring that their use can be detected through bioanalytical testing. The present study provides the determination of the in vitro Phase I metabolism of one such compound, PX-1 (5F-APP-PICA), and appropriate markers to demonstrate human consumption. PX-1 was incubated with human liver microsomes, followed by analysis of the… 

Phase I-metabolism studies of the synthetic cannabinoids PX-1 and PX-2 using three different in vitro models

PX-1 and PX-2 in vitro metabolites were revealed comprehensively by liquid chromatography–high-resolution mass spectrometry measurements and it is shown that all three in vitro assays are suitable for predicting metabolic pathways of synthetic cannabinoids.

In Vitro Metabolic Profile Elucidation of Synthetic Cannabinoid APP-CHMINACA (PX-3).

In vitro phase I metabolism of indazole carboxamide synthetic cannabinoid APP-CHMINACA yielded 12 metabolites, encompassing 7 different metabolite classes, and it is proposed that metabolites M1, M2.1 and M6 are the most appropriate markers to determine consumption of APP- CHMINACA.

Metabolic Profiling of Synthetic Cannabinoid 5F-ADB and Identification of Metabolites in Authentic Human Blood Samples via Human Liver Microsome Incubation and Ultra-High Performance Liquid Chromatography/High-Resolution Mass Spectrometry.

The results demonstrate that it is imperative that synthetic cannabinoid assays screen for pharmacologically active metabolites, especially for drugs with short half-lives, and propose that M1 and M5 are appropriate markers to include in laboratory blood tests screening for 5F-ADB.

Defining Steric Requirements at CB1 and CB2 Cannabinoid Receptors Using Synthetic Cannabinoid Receptor Agonists 5F-AB-PINACA, 5F-ADB-PINACA, PX-1, PX-2, NNL-1, and Their Analogues.

In vitro binding affinities and functional activities at cannabinoid type 1 and 2 receptors (CB1 and CB2, respectively) were determined for all the library members using radioligand competition experiments and a fluorescence-based membrane potential assay, providing insights regarding structural contributions to the cannabimimetic profiles of 17, 18, 19, and 20.

Overview of the major classes of new psychoactive substances, psychoactive effects, analytical determination and conformational analysis of selected illegal drugs

Abstract The misuse of psychoactive substances is attracting a great deal of attention from the general public. An increase use of psychoactive substances is observed among young people who do not

Clinical and Forensic Toxicological Aspects of Synthetic Cannabinoids: A Narrative Review and Update

  • Medicine
  • 2020
Like natural cannabinoids, the SCs abuse/poisoning has serious and life-threatening effects in abuser and suitable measures for information to the public and health care professionals for prevention of SCs Abuse are recommended.

Assessment of Synthetic Cannabinoid FUB-AMB and its Ester Hydrolysis Metabolite in Human Liver Microsomes and Human Blood Samples by UHPLC-MS/MS.

The authors propose that M1 is a reliable marker for inclusion in laboratory blood screens for FUB-AMB, and suggest that synthetic cannabinoid laboratory assay panels include metabolites, especially known or potential pharmacologically active metabolites, particularly for compounds with short half-lives.



Cytochrome P450-Mediated Oxidative Metabolism of Abused Synthetic Cannabinoids Found in K2/Spice: Identification of Novel Cannabinoid Receptor Ligands

Test the hypothesis that JWH-018 and its fluorinated counterpart AM2201 are subject to cytochrome P450 (P450)-mediated oxidation, forming potent hydroxylated metabolites that retain significant affinity and activity at the cannabinoid 1 (CB1) receptor.

In vitro Phase I metabolism of indazole carboxamide synthetic cannabinoid MDMB-CHMINACA via human liver microsome incubation and high-resolution mass spectrometry.

The authors propose that CHM-monohydroxylated metabolites specific to MDMB-CHMINACA are the most suitable candidates for implementation into bioanalytical assays to demonstrate consumption of this synthetic cannabinoid.

Synthesis and Pharmacological Profiling of the Metabolites of Synthetic Cannabinoid Drugs APICA, STS-135, ADB-PINACA, and 5F-ADB-PINACA.

The synthesis and pharmacological characterization of the major metabolites of two high concern SCs; APICA and ADB-PINACA are presented and suggest that the metabolites of SCs potentially contribute to the overall pharmacological profile of these drugs.

Characteristics of the designer drug and synthetic cannabinoid receptor agonist AM-2201 regarding its chemistry and metabolism.

It is suggested that the amounts absorbed by smoking do not significantly influence the metabolic pattern in urine samples, and the N-(4-hydroxypentyl) metabolite of JWH-018 can serve as a valuable marker to distinguish consume of products containing AM-2201 from Jwh-018 use.

Structure-metabolism relationships of valine and tert-leucine-derived synthetic cannabinoid receptor agonists: a systematic comparison of the in vitro phase I metabolism using pooled human liver microsomes and high-resolution mass spectrometry

The presented pHLM approach proved to be an effective tool for systematic investigation of SMRs enabling in-depth understanding of their phase I biotransformation and facilitating the prediction of suitable analytical targets for urine analysis.

Synthetic cannabimimetic agents metabolized by carboxylesterases.

The identified major metabolites of AB-PINACA and AB-FUBINACA are likely to be useful in documenting drug usage in forensic and clinical screening and improves knowledge in the emerging field of xenobiotic metabolism by esterases.

Metabolic profiling of synthetic cannabinoid 5F-ADB by human liver microsome incubations and urine samples using high-resolution mass spectrometry.

The in vitro metabolism of 5F-ADB was investigated by using pooled human liver microsomes assay and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and identified 20 metabolites formed via ester hydrolysis, N-dealkylation, oxidative defluorination, hydroxylations, dehydrogenation, further oxidation to N-pentanoic acid and glucuronidation or a combination of these reactions in vitro.

In vitro metabolism of the synthetic cannabinoids PX-1, PX-2, and PX-3 by high resolution mass spectrometry and their clearance rates in human liver microsomes.

The metabolic profiles of PX-1, Px-2 and PX -3 provide valuable information for the detection of their metabolites in forensic samples and propose marker metabolites to confirm their use.

Phase I Hydroxylated Metabolites of the K2 Synthetic Cannabinoid JWH-018 Retain In Vitro and In Vivo Cannabinoid 1 Receptor Affinity and Activity

This study proposes that K2's high adverse effect occurrence is due, at least in part, to distinct JWH-018 metabolite activity at the cannabinoid 1 receptor (CB1R), and suggests that metabolites of most drugs, but not the carboxy metabolite, retain in vitro and in vivo activity at CB1Rs.

Comprehensive investigation on synthetic cannabinoids: metabolic behaviour and potency testing, using 5F-APP-PICA and AMB-FUBINACA as model compounds.

A workflow for the comprehensive study of SC consumption is proposed and applied to 5F-APP-PICA and AMB-FUBINACA, based not only on the elucidation of their metabolites but also including functional data by the use of the NanoLuc approach, previously published.