Epimerization Studies of LSD Using 1H Nuclear Magnetic Resonance (NMR) Spectroscopy
S. J. Salamone, Z. Li, A. J. Mcnally, S. Vitone, Rongyi Wu
Journal of Analytical Toxicology October 1, 1997 DOI: 10.1093/jat/21.6.492 via OpenAlex
Summary
AI-generated from the abstractLSD converts to its epimer iso-LSD at temperatures above 37 °C and pH levels over 7.0. At pH 7.0 or higher, a 9:1 ratio of LSD to iso-LSD is reached after one week at 45 °C or two weeks at 37 °C. Starting from iso-LSD, achieving the same 9:1 ratio requires six weeks at 45 °C and pH 9.7, indicating more vigorous conditions are needed. This ratio represents an equilibrium concentration with an equilibrium constant K = 9. The study used proton NMR to follow the reaction by integrating the C-9 resonances of LSD and iso-LSD, appearing as singlets at 6.35 and 6.27 ppm respectively. This is the first quantitative measurement of LSD epimerization by NMR.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Duration | One week at 45°C or two weeks at 37°C for LSD to iso-LSD; six weeks at 45°C and pH 9.7 for iso-LSD to LSD |
| Topics | LSD |
| Keywords | Epimer Proton nmr Analytical chemistry journal Chromatography |
| Citations | 23 |
| Key finding | The equilibrium concentration for LSD to iso-LSD epimerization is a 9:1 ratio (K = 9), achieved at temperatures above 37 °C and pH above 7.0, with iso-LSD requiring more vigorous conditions to reach equilibrium. |
Abstract
A study was conducted to determine the conditions needed to achieve the equilibrium concentration for the epimerization of d-lysergic acid diethylamide (LSD) to iso-LSD. The reaction was followed by integration of the C-9 resonance of LSD and iso-LSD by proton nuclear magnetic resonance (NMR). The C-9 resonance of LSD and iso-LSD appear as singlets at 6.35 and 6.27 ppm respectively. Starting with pure LSD, the conversion to iso-LSD is attained at temperatures above 37 degrees C and pH levels over 7.0. At a pH of 7.0 or higher, the LSD/iso-LSD ratio of 9:1 is achieved after one week at 45 degrees C or two weeks at 37 degrees C. Starting with iso-LSD, the conversion to LSD requires more vigorous conditions. The 9:1 LSD/iso-LSD ratio is attained only after 6 weeks at a temperature of 45 degrees C and a pH of 9.7. At lower pH levels, the reaction proceeds more slowly. The 9:1 LSD/iso-LSD ratio is achieved whether the starting material is LSD or iso-LSD and therefore represents an equilibrium concentration (K = 9). In addition, the more vigorous conditions needed to achieve equilibrium of iso-LSD to LSD demonstrate the difficulty in extraction of the epimerizable proton of iso-LSD. This study is the first to quantitate the epimerization of LSD by NMR techniques and establishes the conditions needed to induce epimerization in solution.