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Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 24,
Number 7, October,
pp. 550-556
Here is where the title stuff goes
Metabolism of
Lysergic Acid Diethylamide (LSD) to 2-Oxo-3-Hydroxy LSD (O-H-LSD) in Human
Liver Microsomes and Cryopreserved Human Hepatocytes
Kevin
L. Klette, Cynthia J. Anderson, and Gregory K. Poch
Navy Drug Screening Laboratory, 34425 Farenholt Avenue, Suite 40, San Diego,
California 92134-7040
Alison C. Nimrod and Mahmoud A. ElSohly
National Center for Natural Products Research, Research Institute of Pharmaceutical
Sciences, School of Pharmacy,
University of Mississippi, University, Mississippi 38677
The metabolism
of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy lysergic acid diethylamide
(O-H-LSD) was investigated in liver microsomes and cyropreserved hepatocytes
from humans. Previous studies have demonstrated that O-H-LSD is present in
human urine at concentrations 16–43 times greater than LSD, the parent
compound. Additionally, these studies have determined that O-H-LSD is not
generated during the specimen extraction and analytical processes or due to
parent compound degradation in aqueous urine samples. However, these studies
have not been conclusive in demonstrating that O-H-LSD is uniquely produced
during in vivo metabolism. Phase I drug metabolism was investigated by incubating
human liver microsomes and cryopreserved human hepatocytes with LSD. The reaction
was quenched at various time points, and the aliquots were extracted using
liquid partitioning and analyzed by liquid chromatography– mass spectrometry.
O-H-LSD was positively identified in all human liver microsomal and human
hepatocyte fractions incubated with LSD. In addition, O-H-LSD was not detected
in any microsomal or hepatocyte fraction not treated with LSD nor in LSD specimens
devoid of microsomes or hepatocytes. This study provides definitive evidence
that O-H-LSD is produced as a metabolic product following incubation of human
liver microsomes and hepatocytes with LSD.
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