Improved LC-MS Detection of Opioids, Amphetamines, and Psychedelics Using TrEnDi.

Area of Science:

• Forensic Chemistry
• Analytical Chemistry
• Mass Spectrometry

Background:

• Analyzing novel psychoactive substances and smuggled drugs presents significant analytical challenges.
• Gas and liquid chromatography coupled to mass spectrometry (MS) are standard for drug analysis.
• Chemical derivatization is crucial for enhancing sensitivity in trace analyte determination.

Purpose of the Study:

• To introduce and evaluate trimethylation enhancement using diazomethane (TrEnDi) for improving MS-based drug analysis.
• To demonstrate TrEnDi's effectiveness in enhancing sensitivity and resolving interferences for various drugs of misuse.
• To assess TrEnDi's applicability in real-world forensic samples.

Main Methods:

• Perimethylation of 13 drugs of misuse using TrEnDi.
• Analysis using mass spectrometry (MS) with enhanced sensitivity detection.
• Utilizing 13C-isotopically labeled TrEnDi reagents to address isobaric interferences.
• Employing an unconventional aprotic solvent system for electrospray ionization.
• Application of TrEnDi to morphine analysis in a urine matrix.

Main Results:

• Successful permethylation of all tested analytes.
• Significant MS sensitivity enhancements (1.2 to 24.2-fold) for 11 compounds.
• Improved reversed-phase chromatographic retention for most derivatized species.
• Resolution of isobaric interferences between three controlled substance pairs using 13C-TrEnDi.
• Detection of TrEnDi-modified amphetamine, while unmodified was undetectable.
• 2.4-fold sensitivity enhancement and 103.1% recovery for morphine in urine.

Conclusions:

• TrEnDi is a versatile derivatization technique that enhances MS sensitivity for a wide range of drugs of misuse.
• The method aids in resolving isobaric interferences and improving chromatographic behavior.
• TrEnDi is applicable to trace analysis in complex matrices like urine, demonstrating its practical utility in forensic workflows.