Metabolism of N1-cyclopropylmethanoyl-lysergicaciddiethylamide (1Cp-Lsd) by Human Liver Microsomes

A newly encountered designer drug “N1-cyclopropylmethanoyl-lysergicaciddiethylamide (1cP-LSD)” is an acylated derivative of LSD. Based on the structural characteristics, 1cP-LSD is expected to be readily metabolized to LSD, which can make it difficult to discriminate between intakes of 1cP-LSD and LSD. In this study, to obtain the fundamental information needed for proving intake of 1cP-LSD, the metabolism experiments were performed using human liver microsomes (HLM). 1cP-LSD and its 10 metabolites were detected in HLM reaction mixtures of 1cP-LSD using liquid chromatography-high resolution-tandem mass spectrometry with a C18 semi-micro column and the time-course changes in concentrations of them were observed during the first 120 minutes of the reactions. The results demonstrated that 1cP-LSD rapidly decreased in microsomal mixtures (half-life time: 5 min) and a metabolic reaction by carboxylesterase, expressed abundantly in liver, was mostly responsible for the decrease. This short half-life of 1cP-LSD implied biological samples such as urine and blood should be collected from suspects as soon as possible after intake for detecting unchanged 1cP-LSD, which can lead to the proof of intake. Four out of 10 microsomal metabolites (hydroxy-, N-desethyl-, N6-desmethyl and N-desethyl-N6-desmethyl metabolites) could also be useful indicators for proving intake of 1cP-LSD since they retain a cyclopropylmethanoyl group. Especially, the N6-desmethyl metabolite appeared to be a more appropriate indicator because it could be detected in microsomal mixtures over longer periods.