Maduramicin [OVA]

Drugs that are used as medicines and also as growth promoters in veterinary care are considered as emerging environmental contaminants and in recent years concern about their potential risk to ecosystems and human health has risen. In this paper we used a method based on liquid chromatography/electrospray tandem mass spectrometry to analyze eight coccidiostatic compounds: diclazuril, dinitrocarbanilide (the main metabolite of nicarbazin), robenidine, lasalocid, monensin, salinomycin, maduramicin and nasarin. Multiple-stage mass spectrometry (MSn) based on the precursor ions [M + Na](+) (polyether ionophores), [M + H](+) (robenidine) and [M - H](-) (diclazuril and dinitrocarbanilide) was used to study the fragmentation of these compounds. MS' data and genealogical relationships were used to propose a tentative assignment of the different fragment ions. Loss of water, decarboxylations, ketone beta-cleavages and rearrangement of cyclic ethers and amide groups were some of the fragmentations observed for these compounds. Liquid chromatography with a sub-2 mu m particle size column was coupled to tandem mass spectrometry (LC/MS/MS) allowing the separation of these compounds in less than 7 min. Method detection limits ranging from 11 to 71 ng L-1 and run-to-run values in terms of relative standard deviation (RSD) (up to 12%) were obtained. Copyright (C) 2009 John Wiley & Sons, Ltd.

RationaleSalinomycin is an ionophore antibiotic with potential anticancer activity. The history of its use in veterinary medicine shows large differences in species susceptibility to its toxicity. At the same time, the results of research to date suggest a correlation between the extent and pathways of ionophore biotransformation and its toxicity. The biotransformation pattern of salinomycin has not been studied so far. MethodsExtracts from culture media of human hepatoma cells (HepG2) exposed to salinomycin were analysed with two mass spectrometry techniques. For the first one, micro-liquid chromatography coupled with a quadrupole time-of-flight (Q-TOF) mass spectrometer was used. In the second approach, high-performance liquid chromatography was coupled with a hybrid triple quadrupole linear ion trap. Both experiments were operated in positive electrospray ionization mode. To identify unknown salinomycin metabolites, information-dependent acquisition was applied. ResultsMetabolites identified with tandem mass spectrometry included hydroxylated, demethylated and hydroxylated-demethylated derivatives, in total 14 compounds. Using high resolution, only eight isomers of hydroxysalinomycin were detected. The efficiency of biotransformation was low, and so was the abundance of the signals; only for two metabolites did the signal exceed 1% of the salinomycin signal. The analysis of fragmentation patterns narrowed the structure combinations but the actual modification site could not be specified. ConclusionsTandem mass spectrometry was more sensitive in the identification of salinomycin metabolites in comparison to the Q-TOF approach. Because of low efficiency of biotransformation of the applied model, the obtained fragmentation data are not sufficient to fully characterize the detected compounds. A study with more metabolically active primary hepatocytes is needed.