New insight into the evaluation of complex mixture biodegradability: an UHPLC-qToF “all-ion MS/MS” acquisition technique for the untargeted and targeted analysis of pharmaceutical formulation biodegradation

UHPLC-qToF analysis is reported here as a modern and reliable spectrometric technique, for a more accurate evaluation of the biodegradation of pharmaceutical formulations that should be considered as complex mixtures of organic compounds interacting with naturally occurring microfauna. The untargeted approach evidences that natural and non-natural compounds are not equally biodegraded even when both passed the requirements of the respirometry test. In particular, we demonstrated that for mixtures containing synthetic non-naturally occurring compounds, a new cluster of derivatives can be detected and in part interpreted by a target analysis. We also demonstrated that the fate of the biodegradation of an active ingredient pure or inserted in a pharmaceutical formulation is not the same, confirming that complex chemical systems should be better analyzed using a holistic approach rather than a reductionistic one. The biodegradation of a pharmaceutical formulation could present a different fate compared to that predicted by considering the biodegradability of each component (the global result is not the sum of the parts). Considering these results, an update of the protocols currently used for the evaluation of the environmental impact of chemicals and chemical mixtures used in our daily life can be proposed, through the use of modern technologies nowadays widely diffused in analytical laboratories.