Wastewater-based epidemiology of non-steroidal anti-inflammatory drugs in six cities of Spain: Consumption patterns, seasonal trends, and the role of refined correction factors

Non-steroidal anti-inflammatory (NSAIDs) pharmaceuticals are one of the most widely used drugs worldwide. Their consumption in Spain experienced an increase from 2020 due to the global pandemic COVID-19, according to prescription packaging sales. However, many of these pharmaceutical products are over-the-counter or not all of the amount sold is consumed. Therefore, wastewater-based epidemiology (WBE) was applied to provide objective and real-time information on their consumption. Seven pharmaceuticals were measured in untreated wastewater collected during one week between December 2020 and December 2021 from seven wastewater treatment plants (WWTPs) in different Spanish cities. The samples were analysed using an analytical methodology based on solid-phase extraction and gas chromatography tandem mass spectrometry with prior derivatization. The concentrations found were converted into population normalized daily consumption considering the daily flow rate, population and correction factors. Refined correction factors have been obtained by a systematic review of all accessible studies, considering the excretion factors of each substance and their stability in the sewer system. The results showed that pharmaceutical consumption was similar in the different WWTPs, with paracetamol, ibuprofen and acetylsalicylic acid being the most consumed with mean values of 7, 41 and 12 g/day/1000 inhabitants, respectively. The estimated NSAID consumption (MD), derived from wastewater analysis, aligned with the dispensing values (DCV), except for ibuprofen and diclofenac showing an overestimation of consumption. Principal component analysis (PCA) revealed the predominant days of the week for each compound. In addition, an increase in consumption was observed in the New Year's Eve week. Overall, these findings demonstrate that WBE provides a reliable and complementary approach for assessing real NSAID consumption patterns in the population.