A major metabolite of LSD, 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD), is a superior marker for identifying LSD use because it appears in urine at concentrations 16 to 43 times higher than LSD itself. Testing a wide range of chemically similar compounds, over-the-counter products, prescription drugs, and other drugs of abuse showed none interfered with detecting O-H-LSD. The metabolite remained stable under refrigerated and frozen conditions within normal urine pH (4.6-8.4), but significant loss occurred at room temperature or higher (24-50°C). These findings support the forensic reliability of liquid chromatography-mass spectrometry for detecting LSD use via O-H-LSD.
The metabolism of LSD into a compound called O-H-LSD occurs in human liver cells. O-H-LSD is found in human urine at 16 to 43 times the concentration of LSD itself, and earlier work ruled out its formation during sample handling or storage. This study incubated human liver microsomes and hepatocytes with LSD and used liquid chromatography-mass spectrometry to analyze the products. O-H-LSD was positively identified in all samples treated with LSD but not in any controls. The results definitively show that O-H-LSD is produced as a metabolic product of LSD in human liver tissue.
Two liquid chromatography methods (mass spectrometry and ion trap mass spectrometry) are compared for detecting 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD), a major LSD metabolite in urine. Both procedures show linear calibration from 0 to 8,000 pg/mL with correlation coefficients above 0.99, and limits of detection and quantitation of 400 pg/mL. Reanalysis of 68 human urine specimens previously positive for LSD found O-H-LSD concentrations averaging about 16 times higher than LSD concentrations. Either method can be adapted for high-volume drug testing, and targeting this metabolite may extend the detection window for LSD use.