A fully automated approach for the analysis of 37 psychoactive substances in raw wastewater based on on-line solid phase extraction-liquid chromatography-tandem mass spectrometry

J Chromatogr A. 2018 Nov 16:1576:80-89. doi: 10.1016/j.chroma.2018.09.038. Epub 2018 Sep 18.


This work presents a multi-residue method for the simultaneous determination of 37 legal and illicit psychoactive substances in wastewater, including the most common illicit drugs (cocaine-related compounds, amphetamine-type stimulants, hallucinogens, opiates/opioids, and cannabinoids), new psychoactive substances (two synthetic cathinones, the synthetic opioid AH-7921, and the arylcyclohexylamine methoxetamine), and legal but controlled psychoactive substances (stimulants, benzodiazepines, antidepressants, sedatives, antipsychotics, and hypnotics). To this end a fully automated analytical approach based on solid phase extraction coupled in series to liquid chromatography tandem mass spectrometry detection (on-line SPE- LC-MS/MS) was used. The methodology developed was validated in terms of linearity, recovery, repeatability, and sensitivity in wastewater. Method linearity was between 0.1 ng/L (or the analyte limit of quantification if higher) and 2,000 ng/L (10,250 ng/L in the case of caffeine). Absolute recoveries were variable (between 5% and 132%), depending on the analyte. However, the use of isotopically labeled compounds corrected for analyte losses during the extraction process and matrix effects (relative recoveries within the range of 80-120%). Repeatability of the method was satisfactory for all analytes, with RSD values lower than 13% for most compounds. Limits of detection and quantification in wastewater were below 7 and 23 ng/L, respectively, for all analytes except lormetazepam (10 and 32 ng/L), caffeine (13 and 44 ng/L), and the cannabinoids 11-nor-9-carboxy- Δ9-tetrahydrocannabinol (18 and 61 ng/L) and 11-hydroxy-Δ9- tetrahydrocannabinol (69 and 228 ng/L). The method was applied to the analysis of wastewater samples collected daily in Barcelona for one week. Twenty-five of the 37 analytes were detected in the samples analyzed. Average concentrations ranged from 7 ng/L in the case of zolpidem to 54 μg/L in the case of caffeine.

Keywords: Drugs of abuse; Liquid chromatography-tandem mass spectrometry; New psychoactive substances; On-line solid phase extraction; Psychotropic pharmaceuticals; Sewage water.

MeSH terms

  • Chemistry Techniques, Analytical / methods*
  • Chromatography, Liquid*
  • Psychotropic Drugs / analysis*
  • Psychotropic Drugs / isolation & purification
  • Solid Phase Extraction*
  • Tandem Mass Spectrometry*
  • Wastewater / chemistry*
  • Water Pollutants, Chemical / analysis*
  • Water Pollutants, Chemical / isolation & purification


  • Psychotropic Drugs
  • Waste Water
  • Water Pollutants, Chemical