The discovery of new biomarkers in urine may improve the monitoring of synthetic drug abuse

A team of researchers from the National University of Singapore (NUS) has developed a new solution to improve drug abuse monitoring by designers. Led by Professor Eric Chan of the NUS Department of Pharmacy, the team identified three new urine biomarkers that could be used to detect the use of ADB-BUTINACA, a new synthetic cannabinoid that is a type of new psychoactive substance (NPS) to recognize. The innovative approach to identifying the biomarkers can be applied to other existing and new synthetic cannabinoids.

NPS are drugs that are supposed to mimic the effects of illegal substances such as cannabis, cocaine, heroin, “ice”, ecstacy and LSD. The intention of the secret laboratories to introduce synthetic cannabinoids with different chemical structures is to circumvent legal prohibitions.

For the past two years, NPS users made up the third largest proportion of drug addicts in Singapore, while synthetic cannabinoids dominated the NPS market in Singapore for the past four years. Since most synthetic cannabinoids are largely metabolized in the body after consumption, they are practically undetectable in urine samples.

Regarding the importance of the team’s research, Prof. Chan said: “Before our study, the metabolism and urinary biomarkers of ADB-BUTINACA were unclear. Our discovery and unique methodology provide support for the forensic fraternity that is constantly being challenged by the advent “of novel synthetic cannabinoids and may also benefit the international public in combating the increasing abuse of this synthetic cannabinoid. This will bring us closer to the goal of a drug-free world. “

The study, carried out in collaboration with the Analytical Toxicology Laboratory of the Singapore Health Sciences Authority, was first published in the journal Clinical Chemistry on August 13, 2021.

New biomarkers for the precise detection of the abuse of synthetic drugs

ADB-BUTINACA is a new synthetic cannabinoid that was first identified in Europe in 2019 and made its way onto Singapore’s drug scene last year. Although three existing metabolites of ADB-BUTINACA are available as reference standards for routine forensic monitoring, they have not been detected in some urine samples from abusers or in lower concentrations. This sparked an impetus to identify other potential metabolites that can be used as urinary biomarkers for the consumption of the cannabinoid.

Rather than using the conventional and more time consuming method of chemical synthesis of metabolites of ADB-BUTINACA, Prof. Chan and his team presented an innovative method for identifying the unique metabolites of the cannabinoid using the concepts of drug metabolism and pharmacokinetics.

The team synthesized key metabolites of ADB-BUTINACA using human liver enzymes in the laboratory to study their disposition and identify new biomarker metabolites in urine. Using this method, a total of 15 metabolites of ADB-BUTINACA and their respective biotransformation pathways in the body were identified for the first time from their studies.

Of the 15 new metabolites, the researchers suggested four as biomarkers for urinary metabolites based on their metabolic stability, including one for which the reference standard is currently available. To diagnose the consumption of ADB-BUTINACA, a panel was developed that contains either one or a combination of these four newly established biomarkers for urine.

In the future, the team plans to expand its current strategy to better understand the disposition of novel metabolites of synthetic cannabinoids by the kidneys and their possible occurrence in the urine.


National University of Singapore

Journal reference:

Sia, CH, et al. (2021) Biomarkers for Urine Metabolites for Detection of Synthetic Cannabinoid-ADB-BUTINACA Abuse. Clinical Chemistry.

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