Liquid chromatography/quadrupole-time-of-flight mass spectrometry with metabolic profiling of human urine as a tool for environmental analysis of dextromethorphan

We use the combination of liquid chromatography/quadrupole-time-of-flight mass spectrometry (LC/Q-TOF-MS) and urine metabolic profiling to find and identify the metabolites of dextromethorphan, a common over-the-counter (OTC) cough suppressant. Next, we use the combination of ion masses, their MS/MS fragmentation, and retention times to determine dextromethorphan and its metabolites in surface water impacted by wastewater. Prior to this study, neither dextromethorphan nor its metabolites have been reported in surface water; in spite of its common use in over 100 various OTC medications. We found that the concentration of the dextrorphan metabolite in surface water greatly exceeded the parent compound by factors of 5–10 times, which reflects the urine profile, where parent compound is approximately <2% of the total excreted drug based on ion intensities. Urine profiling also indicated that glucuronide metabolites are major phase 2 products (92% of the total) in urine and then are completely hydrolyzed in wastewater to dextrorphan and N-demethyldextrorphan, which are phase 1 metabolites—a “kind of reversal” of human metabolism.

► Discovery of dextromethorphan and metabolites in surface water.
► Metabolic profiling to create standards for environmental analysis.
► Finding of un-reported glucuronides of dextromethorphan in urine.
► High accuracy LC/Q-TOF-MS–MS analysis of all metabolites.
► Detailed fragmentation investigation of dextromethorphan and metabolites.