Simultaneous multi-targeted forensic toxicological screening in biological matrices by MRM-IDA-EPI mode

Area of Science:

• Forensic Toxicology
• Analytical Chemistry
• Pharmacology

Background:

• Paediatric intoxications and overdose deaths require accurate drug identification.
• Current toxicological screening methods may lack comprehensive drug coverage or speed.
• Validated analytical approaches are crucial for reliable forensic and clinical toxicology.

Purpose of the Study:

• To develop and validate a novel multi-targeted toxicological screening method.
• To compare the developed method's performance against Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS).
• To assess the method's applicability in real-world paediatric intoxication and forensic cases.

Main Methods:

• Development of a toxicological screening method utilizing Multiple Reaction Monitoring-Information-Dependent Analysis-Enhanced Product Ion (MRM-IDA-EPI).
• Chromatographic separation using a gradient elution on a Kinetex Phenyl-Hexyl column.
• Sample preparation involving deproteinization and enzymatic hydrolysis for diverse biological matrices.

Main Results:

• The method successfully identified 751 drugs and metabolites (704 positive, 47 negative).
• Optimal agreement (100%) was achieved when comparing screening results with LC-MS/MS analysis across all tested matrices.
• The method demonstrated high sensitivity, with cut-offs at the lowest tested concentrations for most analytes.

Conclusions:

• A multi-targeted, fast, sensitive, and specific MRM-IDA-EPI screening method was successfully developed and validated.
• The proposed method demonstrates extensive applicability in various toxicological fields, including paediatric intoxications and forensic investigations.
• The validated method provides a reliable tool for comprehensive drug analysis in complex biological samples.