Epimerization studies of LSD using 1H nuclear magnetic resonance (NMR) spectroscopy.
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.
Salamone
S J
SJ
Roche Diagnostic Systems, Somerville, New Jersey 08876, USA.
Li
Z
Z
McNally
A J
AJ
Vitone
S
S
Wu
R S
RS
D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D008238:Lysergic Acid Diethylamide / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D012997:Solvents; D013237:Stereoisomerism; D013997:Time Factors
D012997:Solvents; D008238:Lysergic Acid Diethylamide