Elucidation of LSD In Vitro Metabolism by Liquid Chromatography and Capillary Electrophoresis Coupled with Tandem Mass Spectrometry*

The in vitro metabolism of LSD by human liver microsomes was investigated using tandem mass spectrometry, high-performance liquid chromatography, and capillary electrophoresis. Two new metabolites, lysergic acid ethylamide (LAE) and 2-oxo-LSD, were positively identified by comparison with reference standards. Other detected metabolites included mono- and trioxylated forms. The major metabolic route is deethylation. In human urine specimens from LSD users, iso-LSD was present at the highest concentration, followed by nor-LSD and isonor-LSD, with low levels of LAE and iso-LAE also found.

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Abstract

The in vitro metabolism of D-lysergic acid diethylamide (LSD) by human liver microsomes was investigated. Tandem mass spectrometric techniques, using precursor and neutral loss scans, were employed in the initial search for drug metabolites. The determination of LSD human liver in vitro metabolites was performed by high-performance liquid chromatography and capillary electrophoresis coupled with tandem mass spectrometry. Two new in vitro metabolites, lysergic acid ethylamide (LAE) and 2-oxo-LSD, were positively identified; their structures were established by comparing with reference standards. Several other possible in vitro metabolites detected were suggested to be mono- and trioxylated metabolites of LSD. The major metabolic route of LSD by human liver microsomes is deethylation. Some results with LSD-positive human urine are presented. Among the LSD-related compounds detected in human urine specimens, iso-LSD was present at the highest concentration, followed by nor-LSD and isonor-LSD. Low concentrations of LAE and iso-LAE were also found in these urine specimens.