Evaluating dextrorphan as a wastewater biomarker for cough suppressant use: A longitudinal study in China
Xue-Ting Shao1, Xin-Dong Ma2, Jing-Long Li3
1State Key Laboratory of Marine Resources Utilization in South China Sea (MRU), Hainan University, No. 58, Renmin Avenue, Haikou, China; College of Environmental Science and Engineering, Dalian Maritime University, No. 1 Linghai Road, Dalian, China; Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, Woolloongabba, Australia.
Abstract:
Coughing often signals respiratory health issues. The use of dextromethorphan, available as an over-the-counter opioid antitussive in China, is largely undocumented. This study evaluates the feasibility of dextromethorphan and its metabolite dextrorphan, as wastewater-based epidemiology (WBE) biomarkers for monitoring dextromethorphan use. To determine their suitability, key criteria including urinary excretion, detectability in wastewater, unique human metabolic source, and stability were applied. Both dextromethorphan and its metabolite dextrorphan are excreted via urine (62.5 % as dextrorphan and 0.5 % as dextromethorphan) hence meet the "excreted in urine" criteria. Both biomarkers were also measured in wastewater meeting the "detectable in wastewater" criteria, and dextrorphan's concentration ratio to dextromethorphan was consistent with its excretion profile suggesting that dextrorphan also meet's the criteria of "unique source: human metabolism". In-sample stability was assessed over 72 h and both biomarkers were deemed as stable. Consequently, employing dextrorphan as a WBE biomarker enables the assessment of temporal and spatial usage trends of dextromethorphan, underscoring its practicality. Additionally, a spatio-temporal investigation across 30 Chinese cities revealed an average dextrorphan consumption of 13 mg/d/1000 inh, closely aligning with China's reported annual production estimate of 12 mg/d/1000 inh. This strong concordance supports the validity of using dextrorphan as a WBE biomarker for estimating dextromethorphan consumption. The consumption of dextromethorphan was higher in northern regions compared to southern regions. Temporally, the consumption of dextromethorphan decreased from 233 mg/d/1000 inh in 2015 to 12.3 mg/d/1000 inh in 2021, but with a notable increase in 2022 (24 mg/d/1000 inh) attributed to the COVID-19 outbreak in China in December 2022. Seasonally, the consumption of dextromethorphan in winter was higher compared to spring. This study confirms the suitability of dextrorphan as a biomarker for assessing dextromethorphan usage, and supports the application of WBE for monitoring population-level use of respiratory OTC medications.
