Persistence of N-oxides transformation products of tertiary amine drugs at lab and field studies

Abstract

This work aimed at studying the formation and persistence of N-oxides transformation products (TPs) of tertiary amine drugs by combining laboratory and field studies relevant for surface water. A monitoring study using passive samplers was first achieved for assessing attenuation of selected pharmaceuticals and their related N-oxides and N-, O-dealkylated TPs (i.e., venlafaxine, tramadol, amisulpride and sulpiride) along a 1.7 km river stretch between two sampling sites. This study revealed the stability of tramadol-N-oxide, amisulpride-N-oxide and the fast dissipation of O-desmethylvenlafaxine-N-oxide, as well as the significance of N-oxidized TPs in comparison to N-dealkylated TPs and parent compounds in river. Lab-scale experiments were then implemented for a better understanding of their mechanisms of formation and degradation under aerobic water/sediment testing and under simulated solar photochemistry. N-oxidation reactions were always a minor transformation pathway under both degradation conditions with respect to N-and O-dealkylation reactions. The amount of generated N-oxides were similar for venlafaxine, tramadol and sulpiride and peaked in the 8.4-12.8% and <4% of their initial concentration (100 μg/L), during photodegradation and biodegradation experiments, respectively. Other transformation pathways such as hydroxylation and α-C-hydroxylation followed by oxidation to amide or dehydration were also identified. Investigated N-oxides TPs (except O-desmethylvenlafaxine-N-oxide) were found stable under solar photolysis and aerobic biodegradation with a very slight reverse reaction to parent compound observed for tramadol-N-oxide and amisulpride-N-oxide. Lab-scale degradation experiments were not able to anticipate the high occurrence levels of N-oxide compounds in the environment. This was most likely due to faster degradation kinetics and/or higher sorption to sediment of parent compounds and dealkylated TPs over N-oxide TPs, resulting in higher relative accumulation of the latter.

Keywords: Biotransformation; Field study; N-oxides; Phototransformation; Tertiary amine.