A new LC-MS-MS method for detecting the LSD metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) in urine is less complex, shorter, and provides cleaner chromatographic characteristics than the existing GC-MS method. All 74 urine specimens containing LSD by GC-MS also contained O-H-LSD at significantly higher concentrations, ranging from 732 to 112,831 pg/ml (mean 16,340 pg/ml). The ratio of O-H-LSD to LSD ranged from 1.1 to 778.1 (mean 42.9). The presence of O-H-LSD at substantially higher concentrations than LSD suggests that analyzing for O-H-LSD as the target analyte using LC-MS-MS will provide a much longer detection window for LSD use than analyzing the parent compound.
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.