Structural annotation of electro- and photochemically generated transformation products of moxidectin using high-resolution mass spectrometry.

Lisa Kotthoff, Sarah-Louise O'Callaghan, Jan Lisec, Tanja Schwerdtle, Matthias Koch

Analytical and bioanalytical chemistry 2020 May

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Moxidectin (MOX) is a widely used anthelmintic drug for the treatment of internal and external parasites in food-producing and companion animals. Transformation products (TPs) of MOX, formed through metabolic degradation or acid hydrolysis, may pose a potential environmental risk, but only few were identified so far. In this study, we therefore systematically characterized electro- and photochemically generated MOX TPs using high-resolution mass spectrometry (HRMS). Oxidative electrochemical (EC) TPs were generated in an electrochemical reactor and photochemical (PC) TPs by irradiation with UV-C light. Subsequent HRMS measurements were performed to identify accurate masses and deduce occurring modification reactions of derived TPs in a suspected target analysis. In total, 26 EC TPs and 59 PC TPs were found. The main modification reactions were hydroxylation, (de-)hydration, and derivative formation with methanol for EC experiments and isomeric changes, (de-)hydration, and changes at the methoxime moiety for PC experiments. In addition, several combinations of different modification reactions were identified. For 17 TPs, we could predict chemical structures through interpretation of acquired MS/MS data. Most modifications could be linked to two specific regions of MOX. Some previously described metabolic reactions like hydroxylation or O-demethylation were confirmed in our EC and PC experiments as reaction type, but the corresponding TPs were not identical to known metabolites or degradation products. The obtained knowledge regarding novel TPs and reactions will aid to elucidate the degradation pathway of MOX which is currently unknown. Graphical abstract.

Citation

Lisa Kotthoff, Sarah-Louise O'Callaghan, Jan Lisec, Tanja Schwerdtle, Matthias Koch. Structural annotation of electro- and photochemically generated transformation products of moxidectin using high-resolution mass spectrometry. Analytical and bioanalytical chemistry. 2020 May;412(13):3141-3152