In vitro metabolic fate of 1-[3-(trimethylsilyl)propanoyl] lysergic acid diethylamide (1S-LSD), a silicon-containing LSD analog.
Forensic toxicology – July 29, 2025
Source: PubMed
Summary
A new silicon-containing drug, 1S-LSD, an LSD analog, surprisingly forms Lysergic acid diethylamide (LSD) early in its in vitro metabolism. Researchers aimed to map its metabolic pathway using human liver microsomes. They identified 62 metabolites, proposing a detailed pathway. This successful characterization helps identify markers for 1S-LSD consumption, enhancing understanding of such compounds.
Abstract
A new lysergic acid diethylamide (LSD) analog has recently been identified, 1-[3-(Trimethylsilyl)propanoyl] LSD (1S-LSD), characterized by a silicon-containing acyl moiety. In the proof of LSD analog consumption, direct detection of the parent compound in urine or blood can be challenging; therefore, characteristic metabolites as consumption markers should be detected. However, the metabolic fate is unclear. This study aimed to characterize the metabolic properties of 1S-LSD. The synthesized 1S-LSD was incubated with human liver microsomes. The obtained metabolites were analyzed using liquid chromatography-quadrupole time-of-flight mass spectrometry. The parent compound was metabolized at a moderately rapid rate, with the early formation of LSD. Sixty-two metabolites were observed, and a metabolic pathway was proposed. The major metabolites were compounds with hydroxyl groups in the 3-silylpropanoyl moiety. Five metabolites were relatively abundant and retained their 3-silylpropanoyl moieties: N-deethylated 1S-LSD (Si04), N-deethylated and silanolized 1S-LSD (Si06), N-deethylated and monohydroxylated 1S-LSD (Si09 and Si11), and silanolized 1S-LSD (Si21). The metabolic fate of 1S-LSD, an abused drug containing silicon, was characterized for the first time. The diverse metabolic pathways will help better understand the metabolic processes of not only 1S-LSD but also N1-acylated LSD analogs and compounds with trimethylsilyl groups. Si04, Si06, Si09, Si11, and Si21 are potential target analytes for proving 1S-LSD consumption.