Pharmacokinetics and metabolomics of the new psychoactive substance 4-chloroethylcathinone

Abstract

Synthetic 4-Chloroethcathinone (4-CEC) is a derivative of cathinone that belongs to one of the more severe abused substances among new psychoactive substances (NPS). Current researches on 4-CEC mainly focus on metabolite identification studies, and there is a lack of researches on pharmacokinetic, tissue distribution and metabolomics studies in vivo. A sensitive and reliable LC-MS/MS assay was developed and validated for the determination of 4-CEC concentrations in plasma and tissue homogenates. According to the pharmacokinetic results, the absorption and elimination of 4-CEC were faster after administration. The Cmax was 1896 ± 876 ng/ml, the peak time Tmax was 10.1 ± 9.2 min, and the elimination half-life t1/2 was 100.4 min. Metabolomics studies showed that the highest concentrations of 4-CEC were found in brain, lung, kidney and liver. The results of tissue biopsy showed that the liver, kidney and brain tissue had a certain degree of damage. After 4-CEC administration, amino acid-related metabolism and biosynthesis, lipid metabolism, niacin and niacinamide metabolism in mice were interfered, suggesting that 4-CEC could cause energy metabolism disorder in mice. The metabolic pathways and toxicity mechanisms related to 4-CEC entry into the body were explained at the overall metabolic level by multivariate data analysis, screening and identification of differential metabolites and metabolic pathway analysis.