Fast Response to Emerging Synthetic Opiates: Recent Updates to the RADIAN ASAP Seized Drug Library

Importance of the Topic

This application note addresses the urgent need for forensic and drug chemistry laboratories to detect newly appearing benzimidazole-derived synthetic opioids. These compounds exhibit high potency, pose significant public health risks, and often escape routine screening workflows. Expanding analytical reference libraries with up-to-date spectral data enables laboratories to keep pace with emerging drug threats.

Objectives and Study Overview

The main goal was to enhance the existing RADIAN™ ASAP seized drug library by incorporating spectral fingerprints for 12 benzimidazole opioids. This update aims to allow rapid, reliable screening of seized materials for these novel substances using a “dip and detect” approach and LiveID™ matching software.

Methodology

• Reference materials for 12 benzimidazole opioids were prepared at 50 µg/mL in methanol.
• RADIAN ASAP direct mass detection was performed in positive ionization mode over m/z 50–600.
• Spectra were acquired at cone voltages of 15, 25, 35 and 50 V to generate comprehensive fingerprints.
• LiveID software employed a reverse-fit model to compare acquired data with library entries, using a match score cutoff of 850 for positive identification.

Used Instrumentation

• RADIAN™ ASAP Direct Mass Detector (Waters Corporation)
• LiveID™ spectral matching software
• Waters Xevo TQ-S Micro tandem mass spectrometer coupled with UPLC for isomer differentiation

Main Results and Discussion

• All 12 benzimidazole opioids produced high match scores between 924 and 999 when re-analysed with the updated library.
• Isomeric pair isotonitazene and protonitazene both matched positively, highlighting that RADIAN ASAP alone cannot resolve these isomers.
• Subsequent UPLC-MRM analysis on a TQ-S Micro system achieved chromatographic separation of isotonitazene and protonitazene by over 0.4 min retention time difference.

Benefits and Practical Applications

• Forensic laboratories can rapidly implement the expanded library for routine seized material screening without extensive method redevelopment.
• Early detection of potent benzimidazole opioids aids in controlling distribution and informing public health responses.
• Library updates are freely available via Waters Marketplace, facilitating rapid dissemination of reference data.

Future Trends and Applications

Ongoing expansion of spectral libraries to include newly reported psychoactive substances will remain critical. Integration of automated library updates, high-throughput ambient ionization techniques, and AI-driven spectral prediction may further enhance rapid response capabilities. Combining direct mass detection with chromatographic separation and orthogonal detectors can improve differentiation of structural isomers.

Conclusion

The addition of 12 benzimidazole opioids to the RADIAN ASAP seized drug library significantly strengthens forensic screening for emerging synthetic opioids. High match scores demonstrate the robustness of the updated reference, while complementary UPLC-MRM methods resolve isomeric ambiguities. This workflow empowers laboratories to keep pace with evolving illicit drug markets.

Reference

1. European Monitoring Centre for Drugs and Drug Addiction; New Psychoactive Substances: Global Markets, Global Threats and COVID-19 Pandemic; 2020.
2. Wood M.; Radian ASAP with LiveID – Fast, Specific, and Easy Drug Screening; Waters Application Note 720007125; 2021.
3. Evans-Brown M. et al.; EMCDDA Technical Report on Isotonitazene; 2020.
4. Advisory Council on the Misuse of Drugs; Review of Evidence on Nitazene and Brorphine-Like Opioids; 2022.
5. DEA Diversion Control Division; Benzimidazole Opioids Evaluation; May 2022.
6. Canadian Centre on Substance Use and Addiction; CCENDU Drug Alert Nitazenes; March 2022.
7. Di Trana A. et al.; Synthetic Benzimidazole Opioids: Emerging Health Challenge; Frontiers in Psychiatry 13:858234; 2022.
8. Lee E. et al.; Updating the RADIAN ASAP Seized Drug Reference Library; Waters White Paper 720007838; 2023.
9. Mistry N.S. et al.; Expansion of MRM Toxicology Screening on Xevo TQ-S Micro; Waters Application Note 720007748; 2022.