**3. Amoxicillin sales and occurrence in water bodies**

Amoxicillin acts against a broad spectrum of gram-positive and gram-negative microorgan‐ isms; therefore, it is used as first-line antibiotic both in human medicine and in veterinary medicine in many different countries [56–59]. Table 1 is listed numbers of data reported of sales of amoxicillin in different countries around the globe.


**Table 1.** Sales of amoxicillin in different countries around the world.

Besides to the numbers of sales and use of this drug that have been mentioned above, amox‐ icillin belongs to a group of drugs that are excreted unchanged in urine and faeces at high rates; therefore, it is likely to find amoxicillin concentrations traces in the environment. Table 2 is listed the occurrence and quantity of amoxicillin that have been found in different water bodies of different countries around the world.



**Table 2.** Occurrence of amoxicillin in different water bodies around the world.

Although amoxicillin is an antibiotic drug highly consumed for human and veterinary medicine, and therefore is expected to be found at a relatively high concentration in wastewater and surface water, it is worth noting that there is no much information available in the literature regarding with its occurrence in environmental compartments. This can be explained by the clear fact that the chemical structure of this compound has an unstable β-lactam ring causing it readily undergo hydrolysis shortly after excretion; moreover, this might be the consequence of the incapability of the analysis to assess the presence of all antibiotic compounds presents in the different samples or even that its concentration in the aquatic media is lower than the limits of detection and quantification of the analytical methods.

#### **3.1. Methods of analysis for amoxicillin**

British, India and US Pharmacopoeia recommended liquid chromatography and potentio‐ metric methods for the analysis of pure amoxicillin in pharmaceutical dosage forms (tablet, capsule, oral suspension and injection) [71–73].

However, the extensive literature survey showed that there are several methods, which can be used for assaying amoxicillin in drug substances, formulation products, biological fluids and environmental water samples, that is ultraviolet spectroscopy methods, colorimetric methods, bienzimetic UV-spectrophotometric methods, polarography methods, spectro‐ fluorometric methods, microbiological assays, enzyme linked immunosorbent assays (ELISA), and high-performance liquid chromatography methods (HPLC) [37].

The literature are reported several high-performance liquid chromatography methods with fluorescence, UV or mass spectrometry detection for the determination of amoxicillin residues in edible tissues of cattle, pig, sheep and goat as well as for cow and sheep milk [75–78].

Table 3 is summarized methods to measure amoxicillin residues in animal tissues that are reported in the literature.


**Table 3.** Methods to measure amoxicillin residues in food animal tissues.

The literature are also reported a few high-performance liquid chromatography methods with fluorescence, UV or mass spectrometry detection for the determination of amoxicillin in effluents and environmental water samples [60, 67]. Table 4 summarises some methods to measure amoxicillin and its degradation products in water samples.

The chromatographic methods for amoxicillin analysis in animal tissues and environmental water samples play a significant role in the regulation of the use of this drug in livestock as


**Table 4.** Methods to measure amoxicillin and metabolites in water samples.

well as in the creation of future regulations and monitoring programs for this drug in effluents from wastewater treatment plants, hospitals and households. Regulatory agencies rely on data generated from these methods to establish regulatory actions. Therefore, it is necessary to develop sensitive, accurate and reliable methods to support regulatory programs.
