New psychoactive substances (NPSs) are emerging at an unprecedented rate, challenging conventional forensic screening strategies. 

Conventional forensic and toxicological screening relies on comparing samples against databases and reference standards. While highly effective for known compounds, these approaches have inherent limitations when compounds are newly emerging, structurally modified, or absent from existing databases. 

This challenge has intensified following a legislative change in the Netherlands. Since July 2025, the Opium Act has been amended with a new list, List IA, appended to List I. Rather than listing individual compounds, List IA applies generic structural definitions to entire classes of compounds, including 2-phenethylamines, synthetic cannabinoids, 4-aminopiperidines and benzimidazole opioids. Consequently, a compound may fall within the scope of List IA despite not having been previously encountered, characterized, or included in a reference database. This creates a specific analytical challenge for forensic laboratories. 

Existing targeted and database screening methods are not built to detect compounds that do not yet exist in reference databases. With List IA now regulating entire structural classes, forensic laboratories need a way to flag unknown candidate compounds that fall within these classes, without relying on a pre-existing reference standard for every possible analogue. 

A screening strategy based on shared structural features could provide a complementary approach to conventional database matching, potentially allowing novel analogues to be flagged before reference standards or library spectra become available.

It is well established that compounds sharing a common core structure often behave similarly when analyzed by mass spectrometry, for example, producing characteristic and predictable fragmentation patterns. This raises the possibility that structurally related NPSs belonging to the same List IA class may share specific, predictable neutral losses during MS fragmentation, even when their complete structures differ.

If such class-specific neutral losses can be identified and systematically screened for, neutral loss scanning could be used as a structure-based screening tool to flag previously uncharacterized compounds potentially belonging to List IA classes, substantially narrowing the search space compared to conventional untargeted screening.

Importantly, a detected neutral loss would not by itself establish the identity of a compound or its legal status. Rather, it would provide structural evidence that can be combined with accurate mass, additional product ions and other analytical information to prioritize compounds for further investigation.

Can neutral loss scanning based on shared structural features within the four classes, be used as a screening approach to flag previously uncharacterized compounds that may fall within the structural classes defined by List IA of the Dutch Opium Act?

Sub-questions

1. Which neutral losses are characteristic of each of the four structural classes covered by List IA?
2. To what extent are these neutral losses conserved across structural analogues within each class?
3. How specific are the identified neutral losses for the respective List IA structural classes, and what potential sources of false-positive signals can be identified?
4. How does a neutral-loss-based screening compare, in terms of sensitivity and specificity, to conventional targeted/database screening for detecting novel NPSs?
5. Can a combination of neutral losses and complementary MS/MS features improve the confidence with which novel candidate compounds can be flagged?

Start date

As soon as possible

Duration

Variable

Team

Verdovende Middelen (Illicit Drugs)

Level of education

HBO/Bachelor/MSc specializing in Chemistry/Analytical Chemistry/Forensic Sciences

Contact

Send your CV and motivation letter to:
i.groeneveld@nfi.nl