Enantioselective Determination of Amphetamine-Type Stimulants in Environmental Waters Using SPE and CE-MS/MS

The growing concern over drug abuse, particularly involving amphetamine-type substances (ATS), has led to their monitoring in environmental waters. These chiral compounds, commonly found in river water and wastewater treatment plant (WWTP) effluents, require analytical methods capable of enantiomeric discrimination, as their enantiomers can exhibit different pharmacological and environmental behaviours. A method based on capillary electrophoresis (CE) coupled with tandem mass spectrometry (MS/MS) was developed using a dual cyclodextrin (CD) system consisting of 0.1% 2-hydroxypropyl-β-CD and 0.1% γ-CD in the background electrolyte (BGE), which enabled baseline resolution of the target enantiomers of the ATS under study. Samples were pretreated with solid-phase extraction using a mixed-mode cation exchange sorbent, ExtraBond SCX. Samples of 100 mL for WWTP influent and 250 mL for river water and WWTP effluent were extracted and then eluted with 5 mL of 5% NH₄OH in methanol. Recoveries ranged between 40% and 67% for all amphetamines studied, with detection limits between 0.1 and 0.8 µg/L. Analysis of environmental samples from the Ebre River and WWTPs in Reus and Tarragona (Catalonia, Spain) confirmed the presence of some of the target compounds. Both enantiomers of 3,4-methylenedioxymethamphetamine (MDMA) were determined in WWTP influents and effluents, whereas R-amphetamine was quantified in an influent sample. No target compounds were detected in the analysed river water samples. These findings demonstrate the potential of the developed chiral CE-MS/MS method for robust enantiomeric profiling in environmental waters, attributed to efficient separation based on differences in effective mobility (µ_eff), electroosmotic flow (µ_eo) and selective interactions with CD chiral selectors. The method showed moderate adherence to green analytical principles, achieving an AGREE score of 0.47. Its environmental advantages include the use of CE, minimal solvent consumption and non-toxic chiral selectors, offering a more suitable alternative to more traditional LC-based methods.