Fate and antibacterial potency of anticoccidial drugs and their main abiotic degradation products

The antibacterial potency of eight anticoccidial drugs was tested in a soil bacteria bioassay (pour plate method), EC50-values between 2.4 and 19.6 mu M were obtained; however, one compound, nicarbazin exhibited an EC50-value above the maximum tested concentration (21 mu M, 9.1 mg L-1). The potency of mixtures of two of the compounds, narasin and nicarbazin, was synergistic (more than additive) with 10-fold greater antibacterial potency of the mixture than can be explained by their individual EC50-values. The influence of pH, temperature, oxygen concentration and light on the transformation of robenidine and salinomycin was investigated. Robenidine was transformed by photolysis (DT50 of 4.1 days) and was unstable at low pH (DT50 of approximately 4 days); salinomycin was merely transformed at low pH, the latter into an unknown number of products. The antibacterial potency of the mixtures of transformation products of robenidine after photolysis and at low pH was comparable with that of the parent compound. Finally five photo-transformation products of robenidine were structural elucidated by accurate mass measurements, i-FIT values (isotopic pattern fit) and MS/MS fragmentation patterns. (C) 2008 Elsevier Ltd. All rights reserved.