Abstract
The drug salinomycin (SAL) is a polyether antibiotic and used in veterinary medicine as coccidiostat and growth promoter. Recently, SAL was suggested as a potential anticancer drug. However, transformation products (TPs) resulting from metabolic and environmental degradation of SAL are incompletely known and structural information is missing. In this study, we therefore systematically investigated the formation and identification of SAL derived TPs using electrochemistry (EC) in an electrochemical reactor and rat and human liver microsome incubation (RLM and HLM) as TP generating methods. Liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS) was applied to determine accurate masses in a suspected target analysis to identify TPs and to deduce occurring modification reactions of derived TPs. A total of 14 new, structurally different TPs were found (two EC-TPs, five RLM-TPs, and 11 HLM-TPs). The main modification reactions are decarbonylation for EC-TPs and oxidation (hydroxylation) for RLM/HLM-TPs. Of particular interest are potassium-based TPs identified after liver microsome incubation because these might have been overlooked or declared as oxidated sodium adducts in previous, non-HRMS-based studies due to the small mass difference between K and O + Na of 21 mDa. The MS fragmentation pattern of TPs was used to predict the position of identified modifications in the SAL molecule. The obtained knowledge regarding transformation reactions and novel TPs of SAL will contribute to elucidate SAL-metabolites with regards to structural prediction.
Highlights
Salinomycin (SAL) is an ionophore antibiotic that shows antibacterial, antifungal, antiparasitic, and antiviral properties [1,2]
The oxidation behavior of SAL and identification of SAL-transformation products (TPs) was studied by two different settings: First, the online-mode consisting of an electrochemical reactor (ECR) coupled to an ESI-source of a high-resolution mass spectrometry (HRMS), and, secondly, an offline set-up combining ECR and Liquid chromatography (LC)-HRMS to obtain further information regarding structural proposals of the generated TPs
The online ECR/HRMS set-up led to 11 EC-TPs occurring by applied potential
Summary
Salinomycin (SAL) is an ionophore antibiotic that shows antibacterial, antifungal, antiparasitic, and antiviral properties [1,2]. SAL is commercially used as a veterinary drug to treat and prevent coccidiosis in poultry farming. SAL shows potential as growth promoter in modern animal husbandry (usage not allowed in the EU). The chemical structure of SAL consists of a polyether skeleton with five polyether rings. Similar to other ionophore antibiotics, SAL has a carboxylic group and an ether-ring with a hydroxy-group in terminal positions [1,4]. These specific structural properties lead to the occurrence of a pseudo cyclic SAL complex with metal cations
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.