Determination of lysergic acid diethylamide (LSD), iso-LSD, and N-demethyl-LSD in body fluids by gas chromatography/ tandem mass spectrometry

Article abstract of DOI:10.1021/ac00038a014

Procedures for detection and quantitation of lysergic acid diethylamide (LSD), iso-LSD, and N-demethyl-LSD by capillary chromatography/tandem mass spectrometry (GC/MS/MS) are presented. Several methods for derivatization, sample introduction, and ionization, in combination with mass spectrometry/mass spectrometry (MS/MS), have been evaluated for overall ionization efficiency and product-ion sensitivity and specificity. Fragmentation pathways derived from low-energy collision-induced dissociation (CID) spectra of protonated LSD, and the protonated trimethylsilyl derivatives of LSD (LSD-TMS) and deuterium-labeled analogs of LSD, have been proposed. Principal dissociations primarily involve the amide and piperidine-ring moieties in which losses of CH₃ radical, CH₃NH₂, CH₃NCH₂, diethylamine, diethylformamide, and N,N-diethylpropenamide from MH⁺ are observed. Positive-ion ammonia chemical ionization and subsequent MS/MS analysis of the protonated molecules (MH⁺) of the trimethylsilyl (TMS) derivatives of LSD, iso-LSD, and N-demethyl-LSD provide a high degree of specificity for identification of these compounds in urine or blood at low-pg/mL concentrations. Negative-ion chemical ionization and GC/MS/MS analysis of the molecular anion (M^-) of the trifluoroacetyl (TFA) derivative is well suited for trace-level identification of N-demethyl-LSD, a metabolite of LSD.