Biomarkers for diagnosing intake of OXIZID synthetic cannabinoids

NUS pharmaceutical scientists have successfully identified the urinary biomarkers of an emerging OXIZID subclass of synthetic cannabinoids to monitor potential abuse.

In the past decade, the abuse of new psychoactive substances, particularly their synthetic cannabinoids subclass, has posed a significant risk to public health. While governments impose legislative bans to mitigate the threats to society, illicit manufacturers have produced novel subtypes of synthetic cannabinoids to evade forensic detection. This is demonstrated by the recent emergence of a novel class of synthetic cannabinoids termed as OXIZIDs. The OXIZIDs possess a unique molecular scaffold which is unregulated by existing laws, resulting in their potential abuse.

Synthetic cannabinoid consumption is often identified via the detection of biomarkers in the abusers’ urine samples. These biomarkers are often metabolites of the original synthetic cannabinoid consumed, as these cannabinoids are known for their rapid and extensive metabolism in the human body. For the OXIZIDs, little is known about their metabolite profiles, and their associated biomarkers have not been established yet. This poses a challenge to forensic toxicologists in their attempts to identify OXIZID abusers.

A research team led by Prof Eric CHAN from the Department of Pharmacy, National University of Singapore, had collaborated with the Analytical Toxicology Laboratory, Health Sciences Authority (HSA), Singapore to investigate the key metabolic properties and identify urinary biomarkers of four OXIZID analogues, specifically BZO-HEXOXIZID, BZO-POXIZID, 5F-BZO-POXIZID and BZO-CHMOXIZID. The team built on their previously developed strategy, which couples in vitro biosynthesis of OXIZID metabolites with a comparison and analysis of anonymous urine samples from suspected drug abusers. Their findings were published in Clinical Chemistry.

For each OXIZID analogue, the team started by identifying 12-16 major metabolites, and then narrowed down the selection to three metabolites which could serve as reference urinary biomarkers to detect OXIZID consumption (see Figure). This research outcome will facilitate the work by drug enforcement agencies worldwide in monitoring the prevalence of OXIZID abuse. As part of the study, the team has also determined the critical enzymes responsible for major metabolic pathways involved in the rapid metabolism of OXIZIDs. These findings are important for understanding the toxicological implications of OXIZID consumption.

Prof Chan said, “In collaboration with HSA, our laboratory has been conducting timely research to establish urinary biomarkers for diagnosing the illicit use of emerging synthetic cannabinoids globally. Our work is a testimony of the importance of multi-disciplinary research, specifically in forensic and pharmaceutical sciences, in developing innovative solutions to solve real-world problems.”

HSA has applied the research findings in routine analysis to monitor OXIZID consumption in Singapore. The team intends to continue their analytical approaches to tackle future emerging synthetic cannabinoids.

Figure shows the metabolic processes involved in the human body following the consumption of OXIZID synthetic cannabinoids. In the liver, the OXIZIDs are biotransformed into metabolites by drug-metabolising enzymes. Parent OXIZIDs and mono-hydroxylated metabolites are excreted in the urine and these can serve as biomarkers to detect OXIZID consumption.

Reference

Lee KZH; Wang Z; Fong CY; Goh EML; Moy HY; Chan ECY*, “Identification of Optimal Urinary Biomarkers of Synthetic Cannabinoids BZO-HEXOXIZID, BZO-POXIZID, 5F-BZO-POXIZID and BZO-CHMOXIZID for Illicit Abuse Monitoring” CLINICAL CHEMISTRY DOI: 10.1093/clinchem/hvac138 Published: 2022.