A highly sensitive UHPLC-MS/MS method for determining 15 designer LSD analogs in biological samples with application...

Area of Science:

• Forensic Chemistry
• Analytical Chemistry
• Pharmacology

Background:

• The rise of "designer psychedelics" (LSD analogs) in illicit markets necessitates advanced detection methods.
• Recreational use of these novel psychoactive substances (NPS) is increasing globally.
• Existing methods struggle with the trace determination and isomeric separation of these compounds in biological matrices.

Purpose of the Study:

• To develop and validate a highly sensitive UHPLC-QqQ-MS/MS method for trace determination of LSD and its designer analogs.
• To enable simultaneous separation of structural isomers for accurate identification.
• To assess the stability of LSD analogs in various biological samples under different storage conditions.

Main Methods:

• Ultra-High-Performance Liquid Chromatography coupled with tandem Mass Spectrometry (UHPLC-QqQ-MS/MS) for sensitive quantification.
• Liquid-liquid extraction (LLE) of biological samples (blood, urine, plasma, serum) using ethyl acetate.
• Multiple Reaction Monitoring (MRM) mode for quantification with LSD-d3 as internal standard.

Main Results:

• Achieved a limit of quantification (LOQ) of 0.5 pg/mL for all target analytes, representing the highest sensitivity to date.
• Demonstrated excellent precision (<15.8%) and accuracy (<±14.4%) for the developed method.
• Identified NaF as an effective preservative for stabilizing LSD analogs and preventing degradation during sample storage.

Conclusions:

• The validated UHPLC-QqQ-MS/MS method provides a robust tool for the trace analysis of LSD analogs in forensic and clinical settings.
• The method's high sensitivity and specificity aid in the detection of emerging illicit designer drugs.
• Proposed fragmentation patterns using QTOF-MS/MS can assist in identifying novel designer LSD analogs.