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), EC(50)-values between 2.4 and 19.6 microM were obtained; however, one compound, nicarbazin exhibited an EC(50)-value above the maximum tested concentration (21 microM, 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 EC(50)-values. The influence of pH, temperature, oxygen concentration and light on the transformation of robenidine and salinomycin was investigated. Robenidine was transformed by photolysis (DT(50) of 4.1 days) and was unstable at low pH (DT(50) 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.
Hansen
Martin
M
Section of Toxicology and Environmental Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. mah@farma.ku.dk
Krogh
Kristine A
KA
Brandt
Asbjørn
A
Christensen
Jan H
JH
Halling-Sørensen
Bent
B
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001681:Biological Assay / Q000379:methods; D002627:Chemistry, Physical; D003049:Coccidiostats / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D010775:Photic Stimulation; D010782:Photolysis; D011714:Pyrans / Q000737:chemistry / Q000494:pharmacology; D012370:Robenidine / Q000494:pharmacology; D012988:Soil Microbiology; D000095662:Polyether Polyketides
D000900:Anti-Bacterial Agents; D003049:Coccidiostats; D011714:Pyrans; D012370:Robenidine; C010327:salinomycin; D000095662:Polyether Polyketides