Monitoring the dynamics of ketamine analogues use in China through wastewater analysis: The emergence of 2-FDCNEK and 2-MDCK

Abstract

Ketamine analogues are rapidly emerging around the world and are considered one of the new psychoactive substances (NPS) of greatest concern. However, little is known about their actual use at the community level and their evolution on the drug market. Wastewater-based epidemiology is a useful tool to explore the profile of NPS use. Influent wastewater samples were collected from 21 cities in Southwest China between 2022 and 2023, and ketamine analogues were determined by liquid chromatography-tandem mass spectrometry. Results showed that five ketamine analogues were detected in at least one wastewater sample from 19 cities, of which four new analogues were found in wastewater for the first time. 2-fluoro deschloro-N-ethyl-ketamine (2-FDCNEK) was the most frequently detected analogue, with a population-normalized mass load of up to 3.18 mg day−1 1000 inh−1. The remaining analogues were detected less frequently, with mass loads of almost below 1 mg day−1 1000 inh−1. 2-fluoro deschloroketamine (2-FDCK), which was classified as a controlled substance in 2021, showed an evident downward trend. Furthermore, 2-(methylamino)-2-(2-methyphenyl)-cyclohexanone (2-MDCK) disappeared within a short period, whereas 2-FDCK and 2-FDCNEK persisted over the two-year observation period, suggesting that ketamine analogues containing halogen atoms on the phenyl group may have psychoactive effects similar to those of ketamine, with a high potential for abuse. These findings highlight the importance of wastewater analysis in monitoring the dynamic profile of NPS use, providing valuable information for authorities to take measures to prevent the rapid spread of NPS and minimize health risks.