Forensic drug analysis (police, customs, forensic medicine) has faced new challenges in recent years. One reason for this is the newly emerged phenomenon of new psychoactive substances (NPS). But also the easy accessibility now provided by online trade to synthetic drugs and other products whose distribution is actually protected. These include prescription drugs, doping agents or so-called lifestyle drugs, such as: Viagra. The trade of these substances represents a threat not only to the consumers, but also to the people who come into contact with the goods during the trade (e.g. customs officials or mail order employees). 

Currently, 1-2 new substances appear on the market every week. Their structure and effect on the body are initially unknown. When a new substance appears for the first time, the chemical structure must first be determined exactly (structure elucidation). This requires not only experienced and well-trained personnel but also equipment with very expensive devices, e.g.: high-quality nuclear magnetic resonance (NMR) and mass spectrometers (MS). Such conditions are only available in a few competence centers, which also include the Forensic Science Institute of the German Federal Criminal Police Office. Laboratories that do not have these capabilities send their substances, which are not identifiable for them, to the competence centers. These centers perform the structure elucidation and provide the analytical data (spectra). With these spectra, the next time the substances appear, virtually all laboratories are then able to make the identification themselves by "simple" spectra comparison. 

The "NPS VeriQon" project proposed here is based on the "NPS Data Hub" and "ADEBAR" projects.

• The NPS Data Hub platform is already established globally on all continents at virtually all major forensic laboratories (currently about 500). 
• Analytical data for currently about 5000 relevant substances have already been compiled. 
• This data collection also provides an up-to-date, comprehensive picture of the situation and serves as an early warning system to prevent harm to the population from new "active substances". 
• The NPS Data Hub has several interfaces to other portals. The system is variable and easily adaptable to further interfaces.

One of the greatest challenges in the characterization and identification of chemical substances is the consistent and reliable validation and verification of analytical data in order to be able to derive conclusive statements. The urgent need for a holistic validation system is repeatedly described in the community as the most important task for the coming years, for example in the ENFSI Drugs Working Group's package of measures, or also at the "Online Symposium for Seized Drug Analysis" held in January 2021 with over 2000 participants. The problem also exists in many other areas of chemical analysis, such as research on new drugs, flavors, and ingredients for the food, beverage, as well as cosmetics industries. 

The global exchange of analytical data from laboratories worldwide provides the basis for the rapid and reliable identification of a new substance. The NPS Data Hub already provides global access to an extensive database of psychoactive and other proprietary substances. However, the exchange of data needs to be expanded even further to include newly emerging substances worldwide.

Another challenge for forensic science is the effort to make the identification of a substance mandatory with an uncertainty amount. If this would make sense at all, there is no statistical basis for it so far. 

The project NPS VeriQon aims to address exactly these challenges for rapid and reliable identification of psychoactive substances. For this purpose, a holistic validation system is to be developed taking into account the essential and relevant analytical techniques (NMR, MS, IR, Raman), which would represent a completely new innovation. The basis for the planned data validation and extension is the "NPS Data Hub", which already has a very good, but not validated data base. These data from the structural elucidations already performed are to be validated using automated tools through intelligent data matching as well as artificial intelligence (AI) and quantum chemical simulations. This validation should enable the identification of the substances in a court-proof manner. If this cannot be ensured by the automated validation workflow for all structural elucidations performed, a pool of experts will be used downstream for these cases.

The necessary basic data for the project will be provided by the project partners, also in cooperation with the international partners in forensic technology (acquisition of sample material, manual structure elucidation, generation of comparison spectra, ...). The computer-aided simulations of the spectra serve on the one hand to verify the experimental data and to supplement missing or still outstanding measurement data, and on the other hand to characterize potentially emerging new substances before they appear on the market. It is important to note that quantum-chemically calculated spectra are only derived from elementary laws of nature; different arrangements of mobile molecules (so-called conformations) result in an "overall spectrum". Normally, experts have to generate these arrangements, check them, and make a trade-off between computational effort and accuracy. We aim to automate this process to obtain spectra for a large number of structures at reasonable computational cost without substantial human intervention. 

The development of interfaces to mobile spectrometers will also enable the identification of potentially hazardous substances directly at the point of use by comparing a measured spectrum with the measured and simulated spectra in the NPS Data Hub. 

Another effort represents the development of an analytical method to distinguish stereoisomers of narcotics.

The NPS VeriQon project thus also accelerates the structural elucidation and identification of previously unknown active ingredients. As a result, these substances can be taken out of circulation more quickly and effectively. The validation and simulation methods developed within the framework of NPS VeriQon can subsequently be used without difficulty in other areas of chemical analysis.

In addition, for the first time a comprehensive and valid contribution to the discussion on the indication of uncertainties of substance identifications will be provided. The basis for this is the already existing data base, which will be further expanded in the project. For this purpose, rules have to be established as to when an identification is to be considered unambiguous. It also needs to be clarified whether it makes sense to specify uncertainty amounts at all. 

If yes, it would have to be clarified how this is to be determined validly and what this reflects in terms of meaningfulness. If not, valid scientific justifications would have to be provided. This study thus represents an important contribution to forensic analytics and will help to better classify the evidentiary value of identifications and provide a tool that underpins structural clarifications performed.

 

We would like to expand the NPS Data Hub within the framework of the NPS VeriQon project so that 

• Crime scene units, customs and logistics service providers can quickly examine suspicious substances (for example NPS) for hazard potential and/or suspected crimes using Raman spectroscopy, 
• police authorities at national and international level can identify spectra of newly emerging subtances on the basis of validated spectra from our libraries in order to be able to prove violations of the law in court, 
• errors due to incorrect structure attributions are avoided, and 
• forensic institutes receive an effective, easy-to-use tool for the structure elucidation of new psychoactive substances that exceeds the performance of standardized structure elucidation systems and makes the best possible use of the existing database.

The preceding figure shows the cycle for analytical data for newly emerging compounds (1). First, a complex structure elucidation should be performed in a reference laboratory using several techniques (e.g.: NMR and MS) (2). Among others, this is also done on a large scale by the ADEBAR project. The analytical data (spectra) are uploaded to the NPS Data Hub and are thus immediately visible to all laboratories. Additional spectra can also be added to the data set from other laboratories (3). 

The additional spectra can be acquired with the same technique under different measurement conditions or with a completely different technique (e.g.: IR or Raman). Missing spectra can also be completed by quantum chemical simulations. The data available in the NPS Data Hub are generally not yet considered validated. However, the validation status is clearly marked here to inform users of the reliability of the data.

Spectrum validation is to be performed by the tools to be developed in this project (4). Evaluation criteria to be developed will indicate whether spectra are to be considered validated or not. The more spectra of different techniques are available for a sample, the more reliable the validation can be performed. In addition, complex data validations are to be supported by spectra simulated on the basis of quantum chemistry, since no manual signal-structure assignments are necessary here. 

The validated data will then be collected in spectra libraries for each relevant technique and distributed to laboratories for steady-state use in routine operations (5). This is the responsibility of the ENFSI Drugs Working Group, in which the applicant also has leading representation. 

Substances can then be reliably identified in all the laboratories of the world by comparison with the spectra of the libraries (6). Less expensive equipment can then be used, such as IR or Raman spectrometers. In addition, the NPS VeriQon project will, for the first time, make it possible to use mobile measuring devices to examine suspicious samples during shipping or at a crime scene, also for the multitude of new substances that have been endangering frivolous consumers and also professionals charged with logistics and law enforcement in recent years. This will make validated measurement data, enriched with calculated comparative data, useful for crime scene work and the prevention of immediate dangers.

The plausibility checks used so far have the major disadvantage that only one analytical technique is considered, but not the overall picture of the different measurement methods. NPS VeriQon offers for the first time an unambiguous structure verification by combining several techniques. The workflow should thus then provide unambiguous factual evidence that will also stand up in court (7).