Detection of metabolites of lysergic acid diethylamide (LSD) in human urine specimens: 2-oxo-3-hydroxy-LSD, a prevalent metabolite of LSD

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.

Study at a glance

Abstract

Seventy-four urine specimens previously found to contain lysergic acid diethylamide (LSD) by gas chromatography-mass spectrometry (GC-MS) were analyzed by a new procedure for the LSD metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) using a Finnigan LC-MS-MS system. This procedure proved to be less complex, shorter to perform and provides cleaner chromatographic characteristics than the method currently utilized by the Navy Drug Screening Laboratories for the extraction of LSD from urine by GC-MS. All of the specimens used in the study screened positive for LSD by radioimmunoassay (Roche Abuscreen). Analysis by GC-MS revealed detectable amounts of LSD in all of the specimens. In addition, isolysergic diethylamide (iso-LSD), a byproduct of LSD synthesis, was quantitated in 64 of the specimens. Utilizing the new LC-MS-MS method, low levels of N-desmethyl-LSD (nor-LSD), another identified LSD metabolite, were detected in some of the specimens. However, all 74 specimens contained O-H-LSD at significantly higher concentrations than LSD, iso-LSD, or nor-LSD alone. The O-H-LSD concentration ranged from 732 to 112 831 pg/ml (mean, 16340 pg/ml) by quantification with an internal standard. 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 the analysis for O-H-LSD as the target analyte by employing LC-MS-MS will provide a much longer window of detection for the use of LSD than the analysis of the parent compound, LSD.