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Many pharmaceuticals and drugs of abuse released from wastewater treatment plants are chiral compounds. As our research expanded to include drugs of abuse in wastewater, we identified a unique analytical challenge: the enantiomers of tramadol and O-desmethylvenlafaxine overlap and cannot be adequately separated using conventional approaches. In collaboration with the Hopkins Lab in Chemistry at the University of Waterloo, a new two-dimensional chiral LC × DMS mass spectrometry method was developed to successfully separate and analyze these compounds. This collaborative work was featured on the cover of Analyst.