A Collaborative Approach to New Drug Identification in an Emerging Drug Early Warning System

In North America, the primary drug class leading to mortality in non-medical use is the opioid class, especially illicitly manufactured fentanyl.   However, the drug supply is highly inhomogeneous, and fentanyl is frequently used along with other drugs usually without the fiull awareness of the user.  The other drugs co-ingested with fentanyl include designer benzodiazepines, stimulants, and other novel synthetic opioids.  Other drugs that can have pharmacological interactions include adulterants and cutting agents such as the veterinary tranquilizers xylazine, and medetomidine.  Given how the supply changes geographically and over time, as new drugs and cutting agents appear and disappear rapidly, reliance on user self-report of what drugs they have ingested is uneliable and furthermore exposes the users to increased risk of unintended use of other drug classes.  Laboratory testing practices have historically relied on targeted testing for known drugs but the appearance of novel synthetic drugs and psychoactive substances requires a different approach that includes monitoring for known and emerging drugs, but also surveillance and reactive testing scope expansion to be able to detect the emergence of new drugs, and track their proliferation and geographic spread.

This presentation will describe a collaboration between a large reference laboratory that provides forensic and clinical testing for clinicians, drug treatment professionals, death investigators, law enforcement agencies, with a partner research organization that applies non-targeted testing methods to biological samples to be able to identify drugs that have not previously been identified or recognized in the drug supply.

The workflows consists of aggressive maintainance of an up to date mass spectral database of new drug classes, reanalysis of deidentified discarded biological samples from hospitals, and coroners and medical examiners, looking for these new substances, and identifying them using various data analytic techniques.  Once a new substance is identified, a standard is prepared and is added to an out of scope library for the reference laboratory to be able to surveil for these out of scope findings in their large scale testing.  Leveraging the large volume of samples tested by the reference lab allows the early detection of low prevalence emergent drugs, a key factor for a successful new drug early warning system.   Surveilling for novel opioids allows the rapid development of both screening and confirmatory tests, and dissemination of this information to other testing laboratories, through the research laboratory's network, which publishes and disseminates internationally a quarterly list of recommended scope changes additions and deletions to maintain currency woth these drug market changes.   The process will be illustrated through examples of the potent benzimidazole (nitazene), and designer benzodiazepine drug classes.