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

Capillary gas chromatography/tandem mass spectrometry (GC/MS/MS) methods can detect and quantify LSD, iso-LSD, and N-demethyl-LSD in urine or blood at low-pg/mL concentrations. Derivatization, sample introduction, and ionization techniques were evaluated for efficiency and specificity. Fragmentation pathways from collision-induced dissociation show principal losses from the amide and piperidine-ring moieties. Positive-ion ammonia chemical ionization with MS/MS analysis of trimethylsilyl derivatives provides high specificity for identifying these compounds. Negative-ion chemical ionization with GC/MS/MS of the trifluoroacetyl derivative is suited for trace-level identification of N-demethyl-LSD, a metabolite.

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Abstract

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 trimethylsllyl 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.