Abstract

The consumption of synthetic cannabinoids (SCs) has significantly increased in the last decade and the analysis of SCs and their metabolites in human specimens is gaining interest in clinical and forensic toxicology. A pilot study has been carried out using a combination of an initial last generation gas chromatography-mass spectrometry (GC-MS) screening method for the determination of JWH-122, JWH-210, UR-144) in oral fluid (OF) of consumers and an ultra-high performance liquid chromatography high resolution mass spectrometry (UHPLC-HRMS) confirmatory method for the quantification of the parent compounds and their metabolites in the same biological matrix. OF samples were simply liquid-liquid extracted before injecting in both chromatographic systems. The developed methods have been successfully validated and were linear from limit of quantification (LOQ) to 50 ng/mL OF. Recovery of analytes was always higher than 70% and matrix effect always lower than 15% whereas intra-assay and inter-assay precision and accuracy were always better than 16%. After smoking 1 mg JWH-122 or UR-144 and 3 mg JWH-210, maximum concentration of 4.00–3.14 ng/mL JWH-122, 8.10–7.30 ng/mL JWH-210 ng/mL and 7.40 and 6.81 ng/mL UR-144 were measured by GC-MS and UHPLC-HRMS respectively at 20 min after inhalation. Metabolites of JWH 122 and 210 were quantified in OF by UHPLC-HRMS, while that of UR144 was only detectable in traces. Our results provide for the first time information about disposition of these SCs and their metabolites in consumers OF. Last generation GC-MS has proven useful tool to identify and quantify parent SCs whereas UHPLC-HRMS also confirmed the presence of SCs metabolites in the OF of SCs consumers.

Highlights

  • Synthetic cannabinoids (SCs), as indicated by the name, are an ever-expanding family of compounds synthesized in the laboratory for therapeutic and research purposes, including the qualities of endocannabinoids and phytocannabinoids [1].To date, hundreds of SCs are available on the illicit market being structurally different and categorized into different groups [2]

  • A pilot study has been carried out using a combination of an initial last generation gas chromatography-mass spectrometry (GC-MS) screening method for the determination of JWH-122, JWH-210, UR-144) in oral fluid (OF) of consumers and an ultra-high performance liquid chromatography high resolution mass spectrometry (UHPLC-HRMS) confirmatory method for the quantification of the parent compounds and their metabolites in the same biological matrix

  • After smoking 1 mg JWH-122 or UR-144 and 3 mg JWH-210, maximum concentration of 4.00–3.14 ng/mL JWH-122, 8.10–7.30 ng/mL JWH-210 ng/mL and 7.40 and 6.81 ng/mL UR-144 were measured by gas chromatography mass spectrometry (GC-MS) and UHPLC-HRMS respectively at 20 min after inhalation

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Summary

Introduction

Synthetic cannabinoids (SCs), as indicated by the name, are an ever-expanding family of compounds synthesized in the laboratory for therapeutic and research purposes, including the qualities of endocannabinoids and phytocannabinoids [1]. It can be of importance to investigate SCs pharmacokinetics and their disposition into biological fluids and tissues to understanding the onset, magnitude, and duration of pharmacodynamics effects, so as eventual concentrations associated to intoxications In this regard, we focused on the development and validation of two analytical methods for SCc determination in OF: a last generation gas chromatography–mass spectrometry (GC-MS) method for an initial target analysis of JWH-122, JWH-210 and UR-144 in consumers OF and an ultra-high performance liquid chromatography high resolution mass spectrometry (UHPLC-HRMS) method for a complementary measurement of JWH-122, JWH-210, UR-144 and their metabolites time course in. In the OF sample from JWH-122 consumer, the parent drug presented a peak concentration (Cmax) 4.00 ng/mL (GC-MS) and of 3.14 ng/mL (UHPLC-HRMS) at 20 min (Tmax) after the start of SCs smoking. UR-144 N-(5-OH) was only detected in traces during all the time-course and could never be quantified above the LOQ

Discussion
Chemicals and Reagents
Calibrators and Quality Control Solutions
Synthetic Cannabinoids and Their Metabolites Extraction and Determination
GC-MS Instrumentation
UHPLC-HRMS Instrumentation
Findings
Method Validation
Full Text
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