Three lysergic acid diethylamide (LSD) derivatives were synthesized and characterized. The most stable derivative was selected and covalently linked to polystyrene microparticles through a carrier protein. Two new LSD immunogens were synthesized, generating antibodies that recognize LSD and several major LSD metabolites. A homogeneous microparticle-based immunoassay was developed for detecting LSD in human urine with sufficient sensitivity and specificity for effective screening. The assay's performance was evaluated using precision, cross-reactivity, correlation to the Abuscreen LSD RIA and GC/MS/MS, specificity, and limit of detection.
A photoreactive linker was used to attach lysergic acid diethylamide (LSD) to a carrier protein, keyhole limpet hemocyanin, at multiple sites on the drug. About 35 drug molecules were attached per protein when equal amounts of both were used. Reaction efficiency was severely reduced by buffer components or water. Excess linker, pH, irradiation of the dry matrix without buffer, and the drug-to-protein ratio during photolysis strongly affected efficiency. Antibody specificity data suggested that the drug attached to the protein at positions N1 and N6 of LSD, consistent with the reactivity of the photogenerated aryl nitrene.