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Characterization of iso-LSD metabolism using human liver microsomes in comparison to LSD and its applicability as
Xue Qin Ng1, Evelyn Mei Ling Goh1, Asimah Hamzah1
1Drug Abuse Testing unit, Analytical Toxicology Laboratory, Applied Sciences Group, Health Sciences Authority, 11 Outram Road, Singapore 169078, Singapore.
Abstract:
Urinalysis of lysergic acid diethylamide (LSD) poses a challenge due to its rapid metabolism, resulting in little to no LSD detectable in urine. Instead, its primary metabolite, 2-oxo-3-hydroxy-LSD, is predominantly detected. In this study, we observed several urine profiles with iso-LSD detected together with 2-oxo-3-hydroxy-LSD. Iso-LSD is derived from illicit preparation of LSD as a major contaminant, and it was detected at higher abundance than LSD and 2-oxo-3-hydroxy-LSD in certain urine samples. Therefore, the metabolism of iso-LSD and its potential as a viable urinary biomarker for confirming LSD consumption is of interest. For metabolism studies, LSD and iso-LSD were incubated in human liver microsomes (HLMs) at 0 min, 60 min and 120 min to characterize their metabolites using LC-QTOF-MS. For urinary analysis, 500 µL of urine samples underwent enzymatic hydrolysis and clean-up using supported-liquid extraction (SLE) prior to analysis by LC-QTOF-MS. From HLM incubation study of LSD, the metabolites detected were dihydroxy-LSD, 2-oxo-LSD, N-desmethyl-LSD (nor-LSD) and 2-oxo-3-hydroxy-LSD with LSD levels decreasing significantly throughout all time points, consistent with the existing literatures. For HLM study of iso-LSD, metabolites eluting at retention times after the corresponding metabolites of LSD were detected, with iso-LSD levels showing only a slight decrease throughout all time points, due to a slower metabolism of iso-LSD compared to LSD. These findings corroborate with the urinalysis of 24 authentic urine samples, where iso-LSD with 2-oxo-3-hydroxy-LSD was detected in the absence of LSD. Based on our findings, iso-LSD is commonly detected in urine (18 out of 24 samples) sometimes with traces of possible 2-oxo-3-hydroxy-iso-LSD. The slower metabolism and high detection rate in urine make iso-LSD a viable urinary biomarker for confirming LSD consumption, especially in the absence of LSD and/or 2-oxo-3-hydroxy-LSD.
