Method of Confirmation and Predictive Metabolomics: A Novel Multidimensional Analytical Framework for Characterizing...

Area of Science:

• Forensic Chemistry
• Analytical Chemistry
• Pharmacology

Background:

• New psychoactive substances (NPS) pose challenges for forensic analysis due to their rapid emergence and structural diversity.
• Existing targeted methods struggle with novel compounds, risking false positives or missed detections.
• A robust, non-targeted analytical approach is needed for comprehensive NPS screening and identification.

Purpose of the Study:

• To develop and validate a non-targeted analytical method for the detection and confirmation of NPS.
• To address the limitations of current forensic drug analysis in identifying novel psychoactive substances.
• To enhance the capabilities of forensic laboratories in analyzing emerging drug trends.

Main Methods:

• Ultra-Performance Liquid Chromatography coupled with Quadrupole Time-of-Flight Mass Spectrometry (UPLC-QTOF-MS) was employed.
• Method validation included evaluation of retention time, mass accuracy (±5 ppm), diagnostic fragments, ion ratios, and isotope patterns.
• Predictive metabolomics investigated metabolic transformations in spiked bulk powder and urine matrices.

Main Results:

• The UPLC-QTOF-MS method demonstrated excellent precision, reproducibility, and mass accuracy within ±5 ppm.
• Consistent retention times and diagnostic fragments met SANTE and WADA TD2023IDCR guidelines.
• The limit of confirmation (LOC) was established at 50 ng/mL for all analytes, with significant metabolic transformations identified.

Conclusions:

• The validated UPLC-QTOF-MS method is a powerful tool for rapid NPS detection and confirmation in forensic samples.
• High mass accuracy, non-targeted analysis, and retrospective data analysis offer advantages over traditional methods.
• This approach strengthens forensic investigations by enabling laboratories to keep pace with evolving drug trends.