Source discrimination of drug residues in wastewater: The case of salbutamol.

Abstract

Analytical methods used for pharmaceuticals and drugs of abuse in sewage play a fundamental role in wastewater-based epidemiology (WBE) studies. Here quantitative analysis of drug metabolites in raw wastewaters is used to determine consumption from general population. Its great advantage in public health studies is that it gives objective, real-time data about community use of chemicals, highlighting the relationship between environmental and human health. Within a WBE study on salbutamol use in a large population, we developed a procedure to distinguish human metabolic excretion from external source of contamination, possibly industrial, in wastewaters. Salbutamol is mainly excreted as the sulphate metabolite, which is rapidly hydrolyzed to the parent compound in the environment, so this is currently not detected. When a molecule is either excreted un-metabolized or its metabolites are unstable in the environment, studies can be completed by monitoring the parent compound. In this case it is mandatory to assess whether the drug in wastewater is present because of population use or because of a specific source of contamination, such as industrial manufacturing waste. Because commercial salbutamol mainly occurs as a racemic mixture and is stereoselective in the human metabolism, the enantiomeric relative fraction (EFrel) in wastewater samples should reflect excretion, being unbalanced towards one of two enantiomers, if the drug is of metabolic origin. The procedure described involves chiral analysis of the salbutamol enantiomers by liquid chromatography-tandem mass spectrometry (LC-MS-MS) and calculation of EFrel, to detect samples where external contamination occurs. Samples were collected daily between October and December 2013 from the Milano Nosedo wastewater treatment plant. Carbamazepine and atenolol were measured in the sewage collector, as "control" drugs. Salbutamol EFrel was highly consistent in all samples during this three-month period, but a limited number of samples had unexpectedly high concentrations where the EFrel was close to that observed of the un-metabolized, commercially available drug, supporting the idea of an external source of contamination, besides human metabolic excretion. Results showed that, when present, non-metabolic daily loads could be evaluated indicating an average of 4.12g/day of salbutamol extra load due to non-metabolic sources. The stereoselectivity in metabolism and enantiomeric ratio analysis appears to be a useful approach in WBE studies to identify different sources of drugs in the environment, when no metabolic products are present at useful analytical levels.