An on-line immunoaffinity extraction-coupled column capillary liquid chromatography/tandem mass spectrometry method was developed to detect LSD and its analogs and metabolites in human urine. The system uses three columns and allows direct analysis of diluted urine without pretreatment, eliminating sample handling steps. Concentrations as low as 2.5 parts per trillion of LSD and several analogs were detected in spiked human urine, which is 20-fold lower than the previous limit of detection using solid phase extraction and liquid chromatography/tandem mass spectrometry. The method was also applied to urine specimens from LSD users.
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.