Ocular pharmacokinetics of trimetazidine in the pigmented rat after a single oral administration

Abstract

Amoxicillin (AMX) is a widely used penicillin-type antibiotic whose presence in the environment has been widely investigated, despite its rapid hydrolysis to various degradation products (DPs). In this work, the formation of AMX DPs was studied in various aqueous solutions containing 100 μg mL−1 AMX. Three phosphate buffer solutions, at pH 5, pH 7 and pH 8, and a fourth buffer solution at pH 7 with the addition of the bivalent ions Mg2+and Ca2 as chelating agents, were examined under controlled environmental conditions. In addition, two solutions from natural sources were examined secondary effluents and tap water. The obtained DPs were identified by their MS/MS, UV and NMR spectra (obtained from pure compounds isolated by preparative HPLC) as: AMX penicilloic acid (ADP1/2), AMX penilloic acid (ADP4/5) and phenol hydroxypyrazine (ADP6). Two additional detected DPs AMX 2′,5′-diketopiperazine (ADP8/9), and AMX-S-oxide (ADP3) were reported and discussed in our previous publications. These DPs were then detected in secondary effluent and groundwater from a well located beneath agricultural fields continuously irrigated with secondary effluent. Concentrations in the secondary effluent were: ADP1/2, several micrograms per liter; ADP4/5, 0.15 μg L−1, and ADP8/9, 0.5 μg L−1. ADP6 were detected but not quantified. In the groundwater, only ADP8/9 was detected, at a concentration of 0.03 μg L−1. The detection and quantification of DPs of other investigated drugs is recommended as an integral part of any study, method or technique dealing with pharmaceutical residues in aquatic environments.