In vitro metabolic fate of 1-[3-(trimethylsilyl)propanoyl] lysergic acid diethylamide (1S-LSD), a silicon-containing LSD analog.
Yuki Azuma, Misa Tanaka, Akiko Asada, Takahiro Doi
Forensic toxicology July 29, 2025 DOI: 10.1007/s11419-025-00735-2 via PubMed
Summary
AI-generated from the abstractA new LSD analog, 1S-LSD, which contains a silicon atom, was metabolized in human liver microsomes at a moderately rapid rate, forming LSD early in the process. Sixty-two metabolites were observed, and a metabolic pathway was proposed. The major metabolites had hydroxyl groups on the silicon-containing acyl moiety. Five metabolites that retained this moiety were relatively abundant: 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). These five are recommended as target markers for proving 1S-LSD consumption.
Study at a glance
| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | Human liver microsomes |
| Intervention | 1S-LSD |
| Topics | LSD |
| Keywords | In vitro metabolism Metabolic pathway Silicon-containing drug Detailed pathway |
| Citations | 1 |
| Key finding | 1S-LSD is metabolized to LSD and 62 other metabolites, with five metabolites (Si04, Si06, Si09, Si11, Si21) identified as potential markers for consumption. |
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.