title: New hydrolysis products of the beta-lactam antibiotic amoxicillin, their pH-dependent formation and search in municipal wastewater.
abstract: Amoxicillin (AMX) is a widespread β-lactam-antibiotic and, together with some of its transformation products (TPs) originating from hydrolysis, a known environmental contaminant. To shed light on the abiotic degradation of AMX and the stability of its known TPs, laboratory hydrolysis experiments of AMX were carried out at pH 3, 7 and 11. Not only the rate of hydrolysis but also the pattern of TPs was strongly pH-dependent. The time courses of the obtained transformation products were analyzed by UPLC-HR-QToF-MS. AMX penicilloic acid (TP 1), AMX 2',5'-diketopiperazine (TP 2), AMX penilloic acid (TP 3) and 3-(4-hydroxyphenyl)pyrazinol (TP 4) were found at neutral pH. Surprisingly, the first three were not stable but transformed into 23 yet unknown TPs within three to four weeks. Seven TPs were tentatively identified, based on their product ion spectra and, where possible, confirmed with reference standards, e.g. penicillamine disulfide, 2-[amino(carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid and dehydrocarboxylated amoxicillin penilloic acid. Analysis of samples from municipal wastewater treatment plants confirmed these findings with TP 1 being the dominant TP in the influent and a shift towards TP 2, TP 3 and TP 4 in the effluents. The lab experiments predicted up to 13 consecutive TPs from TP 1, TP 2 and TP 3 under neutral conditions. Their detection from surface waters will be difficult, because their large number and slow formation kinetics will lead to comparatively low environmental concentrations. Nevertheless the abiotic degradation of TP 1, TP 2 and TP 3 to further TPs needs to be considered in future studies of the environmental fate of amoxicillin.
authors.affiliation: UFZ Department of Analytical Chemistry, Helmholtz Center for Environmental Research, Permoserstrasse 15, 04318 Leipzig, Germany; UFZ Department of Ecological Chemistry, Helmholtz Center for Environmental Research, Permoserstrasse 15, 04318 Leipzig, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Hirte
authors.affiliation: UFZ Department of Analytical Chemistry, Helmholtz Center for Environmental Research, Permoserstrasse 15, 04318 Leipzig, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Seiwert
authors.affiliation: UFZ Department of Ecological Chemistry, Helmholtz Center for Environmental Research, Permoserstrasse 15, 04318 Leipzig, Germany; Institute for Organic Chemistry, Technical University Bergakademie Freiberg, Leipziger Strasse 29, 09596 Freiberg, Germany.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Schüürmann
authors.affiliation: UFZ Department of Analytical Chemistry, Helmholtz Center for Environmental Research, Permoserstrasse 15, 04318 Leipzig, Germany. Electronic address: thorsten.reemtsma@ufz.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Reemtsma
mesh_terms: D000658:Amoxicillin / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D006868:Hydrolysis; D013058:Mass Spectrometry; D062065:Wastewater / Q000032:analysis*; D014874:Water Pollutants, Chemical / Q000737:chemistry*
chemical_list: D000658:Amoxicillin; D000900:Anti-Bacterial Agents; D062065:Wastewater; D014874:Water Pollutants, Chemical
keywords: Ampicillin; High resolution mass spectrometry; LC–MS; Resistance; Stability