Determination of benzodiazepines, related pharmaceuticals and metabolites in water by solid-phase extraction and liquid-chromatography–tandem mass spectrometry

• Simultaneous determination of 23 benzodiazepines and related compounds.
• Comparison of SPE cartridges and storage conditions.
• Optimization of the final extract volume considering matrix effects.
• LOQs = 0.1–18 ng L−1 for raw wastewater.
• 10 (of the 23) analytes detected in the samples.

This work presents a method for the simultaneous determination of 23 benzodiazepines, metabolites and related pharmaceuticals (zolpidem, methylphenidate and ritalinic acid) by solid-phase extraction (SPE) followed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Different SPE cartridges were considered: hydrophilic modified reversed-phase (Oasis HLB) and their modified versions containing also a cationic-exchange group (Oasis MCX) or anionic-exchange (Oasis MAX) funcionalities. Stability of analytes and the impact of the final eluate volume on the matrix effects on LC–MS/MS were also considered. In the final method, 100–200 mL of sample are extracted with Oasis MCX (60 mg), eluted with 5 mL of methanol (1.25% NH3) and the eluate concentrated and analyzed by LC–MS/MS. Under these conditions, LOQs were established between 0.1 and 18 ng L−1 for influent wastewater. The use of surrogated deuterated internal standards allows obtaining recoveries in the 84–122% range. Finally the method was applied to determinate the analytes in wastewater and surface water and 10 compounds were detected in the range of 0.5–170 ng L−1, being the ritalinic acid (the main metabolite of methylphenidate) the analyte detected in the highest concentrations.