A new microflow liquid chromatography tandem mass spectrometry method was developed to quantify LSD and its metabolites in human plasma, enabling detection limits of 0.01 ng/mL and separation within three minutes. In a controlled pharmacokinetic study, elimination half-lives of iso-LSD (median 12 h) and LSD metabolites (median 9, 7.4, 12, and 11 h for oxo-HO-LSD, HO-LSD, HO-LSD-gluc, and nor-LSD, respectively) exceeded that of LSD (median 4.2 h). However, screening for these metabolites to extend detection windows in plasma is not constructive because their concentrations are very low.
Three psychoactive stimulants—MDMA, amphetamine, and the new psychoactive substance mephedrone—alter blood metabolites in overlapping but distinct ways. Using plasma samples from controlled human administration studies and liquid chromatography-high resolution mass spectrometry, researchers identified changes in metabolites linked to energy metabolism, steroid biosynthesis, and amino acid pathways. Linoleic acid and pregnenolone-sulfate shifted similarly after intake of all three drugs. Mephedrone produced a metabolic profile more like amphetamine than MDMA, particularly in energy metabolism. These findings could guide future targeted studies on pharmacological actions and help identify biomarkers of drug use.