Improved LC-MS Detection of Opioids, Amphetamines, and Psychedelics Using TrEnDi.
Journal of the American Society for Mass Spectrometry March 5, 2025 Christian A Rosales, Noah A Lepinsky, Wondewossen Gebeyehu et al.
A chemical derivatization technique called trimethylation enhancement using diazomethane (TrEnDi) improves the sensitivity of mass spectrometry for detecting 13 different drugs of misuse. All analytes were successfully permethylated, with 11 showing improved analytical characteristics. Sensitivity enhancements ranged from 1.2-fold to 24.2-fold for psilocybin, and most species showed increased reversed-phase chromatographic retention. Using 13C-isotopically labeled TrEnDi reagents resolved isobaric interference between three pairs of controlled substances. In an unconventional aprotic solvent system for electrospray ionization, TrEnDi-modified amphetamine was easily measured while unmodified amphetamine was not detected. Applied to morphine in real urine, TrEnDi achieved a percent recovery of 103.1% and a 2.4-fold sensitivity enhancement, demonstrating its versatility for trace analysis.