In Vitro Metabolism of 1‐Benzoyl‐Lysergic Acid Diethylamide (1Bz‐LSD) and Identification of a Deethylated Metabolite (1Bz‐LAE) Using a Synthesized Reference Standard

A newly emerged LSD analog, 1-benzoyl-LSD (1Bz-LSD), is rapidly metabolized in human liver microsomes, producing 15 metabolites including LSD itself. One deethylated metabolite remains detectable for a prolonged period, making it a promising target for confirming consumption. This metabolite was chemically synthesized and identified as 1-benzoyl-lysergic acid ethylamide (1Bz-LAE). The synthesis provides a crucial analytical foundation for investigating 1Bz-LSD use, with 1Bz-LAE expected to serve as a valuable marker for detection.

Study at a glance

Abstract

Lysergic acid diethylamide (LSD) analogs represent an emerging class of new psychoactive substances (NPS). These compounds are often rapidly metabolized, making direct detection of the parent compound in biological samples difficult. Therefore, metabolite detection serves as a critical and effective strategy for the confirmation of consumption. However, the metabolic pathways of these analogs remain largely uncharacterized, and synthesized metabolite standards for definitive identification are mostly unavailable. This study investigated the newly emerged LSD analog, (8R)-1-benzoyl-N,N-diethyl-6-methyl-9,10-didehydroergoline-8-carboxamide (1-benzoyl-LSD, 1Bz-LSD), which features a benzoyl moiety at the N1 position. The objectives were to characterize its metabolic fate and synthesize a targeted metabolite analyte for the confirmation of consumption. In vitro metabolism of 1Bz-LSD was examined using human liver microsomes and analyzed through liquid chromatography-quadrupole time-of-flight mass spectrometry. The parent compound was rapidly metabolized, yielding 15 metabolites, including LSD. Among these, a deethylated metabolite was detectable over a prolonged period, indicating its potential as a targeted analyte. To confirm its structure, this metabolite was chemically synthesized and identified as 1-benzoyl-lysergic acid ethylamide (1Bz-LAE). The synthesis and identification of 1Bz-LAE provide a crucial analytical foundation for the investigations of 1Bz-LSD use, with this metabolite anticipated to function as a valuable marker.