Comprehensive Drug Screening for Forensic Toxicology

Importance of the Topic

Forensic toxicology laboratories face a rapidly changing drug environment driven by the emergence of hundreds of novel psychoactive substances. Traditional targeted methods struggle to keep pace with new analogs, lack of reference standards, and retrospective data needs. High resolution mass spectrometry (HRMS) addresses these challenges by enabling broad screening and confident identification even without prior standards.

Study Aims and Overview

This document reviews Waters’ integrated HRMS approach for comprehensive drug screening in forensic toxicology. It outlines the core challenges, describes a complete LC–MS solution with informatics, and presents workflows that support targeted, semi–targeted, and non–targeted screening of over 2000 compounds.

Methodology and Instrumentation

The workflow relies on data–independent acquisition using MSE, capturing precursor and fragment ions for all analytes. Pre–configured processing workflows in the UNIFI application automate library matching, in–silico fragmentation and discovery analysis to detect known drugs and investigate unknown peaks.

Used Instrumentation

• ACQUITY UPLC system for high–performance liquid chromatography
• Xevo G3 QTof mass spectrometer for high resolution, accurate mass detection
• waters_connect informatics platform with UNIFI screening application
• RADIAN ASAP and ACQUITY Rda Detector for rapid seized drug analysis
• Xevo TQ–S Micro and Xevo TQ Absolute for targeted quantitation

Main Results and Discussion

HRMS screening provides comprehensive coverage of illicit, pharmaceutical and emerging NPS due to its ability to detect accurate precursor and fragment masses. The curated library of more than 2000 toxicologically relevant compounds, each verified through rigorous data checks, underpins reliable identifications. The non–targeted acquisition mode supports retrospective analysis as new NPS are discovered.

Benefits and Practical Applications

• Broad, simultaneous screening of large drug panels beyond limits of traditional MRM methods
• Confident identification of known and unknown substances without reference standards
• Retrospective data mining enabled by non–targeted acquisition
• Streamlined sample processing through pre–configured workflows and informatics

Future Trends and Potential Uses

The growth of NPS and increasing demand for rapid forensic results will drive further adoption of HRMS. Future developments may include larger and more dynamic libraries, enhanced in–silico tools, AI–powered discovery workflows and real–time field deployable MS solutions.

Conclusion

An integrated HRMS platform combining advanced UPLC, high resolution accurate mass detection, and dedicated informatics offers forensic toxicology laboratories a robust solution to evolving screening challenges. This approach supports comprehensive, confident, and retrospective analysis critical for modern forensic investigations.