**4. Environmental degradation of amoxicillin**

Several processes can affect the fate and transport of organic compounds in the environment including 1) sorption, 2) biotic transformation and 3) abiotic transformation. The knowledge of the chemical properties and structures of compounds can allow preliminary estimation of their fate and persistence in the environment [91].

Despite that it is well known that β-lactam drugs contain a lactam ring, which is unstable and easily opened by β-lactamases (a widespread enzyme in bacteria) [24] as well as have shown thermal degradation with the hydrolytic cleavage and ultimate mineralisation to CO2 and water [20], there was no detailed information regarding to the transformation of this antimi‐ crobial compound in the environment until recent years.

In 2013, Gozlan et al., suggested a full degradation pathway of amoxicillin in aqueous medium. This starts with the opening of the four-membered β-lactam ring by hydrolysis to yields the intermediate AMX-penicilloic acid, which contains an extra free carboxylic acid group. Also it was reported that various metal ions such as mercury, zinc, cadmium, cobalt and copper might catalyse the degradation of the β-lactam ring. Subsequently depending of the pH of the medium, this intermediate compound could yield two different more stable compounds [89, 92, 93].

At high pH, the lone pair electrons on the amine group of the AMX-penicilloic acid are available for nucleophilic attack on the carbonyl group to yield a six membered stable diketopiperazine ring and the AMX diketopiperazine degradation product [89]. In the other hand, at low pH, the AMX-penicilloic acid suffers a decarboxylation process yielding the AMX penicilloic acid degradation product [89].

Another metabolite of amoxicillin is yield under sunlight irradiation merely as an indirect photolysis process enhanced by the presence of natural photo-sensitisers like humic acids, which activate the oxygen dissolved in water to oxidise the amoxicillin, forming the AMX-Soxide degradation product; also this product is obtained under ozonation process. It is worth noting that the presence of this compound in aquatic environments is of great concern, because the AMX-S-oxide β-lactam ring is still active and may lead to the development of resistant bacteria and even cause other possible health hazards to human and wild and domestic animals [93].

To sum up, it is important to remark that these degradation products are suspected of being more resistant to degradation, and potentially more toxic, than the parent compound [36, 66, 70, 93].
