Abstract
The behaviour of sulfadiazine (SDZ) and its metabolites was investigated by administering the 14C-labelled veterinary drug to fattening pigs. The excretion kinetics were determined after daily collection of manure. Two known metabolites, N-acetylsulfadiazine and 4-hydroxysulfadiazine, and two hitherto unidentified minor metabolites were recovered. Various mass spectrometric techniques such as parent, product ion scans and accurate mass measurement were used. The new compounds were identified as N-formylsulfadiazine (For-SDZ) and N-acetyl-4-hydroxysulfadiazine (Ac-4-OH-SDZ). The identification of SDZ, Ac-SDZ and For-SDZ was confirmed by comparison of the spectroscopic and chromatographic data of the synthesized authentic references. The identification of the hydroxylated compounds 4-OH-SDZ and Ac-4-OH-SDZ was performed by MSn, and accurate mass measurements. Only 4% of the administered radioactivity remained in the pig after ten days and SDZ accounted for 44% of the 96% radioactivity excreted. More than 93% of the labelled compounds were detected and identified in the manure. The key analytical problem, namely a high concentration of matrix in sample extracts, was overcome by advanced measurement techniques and with the use of a suitable internal standard. The mean recoveries for all compounds were ≥96%. Linearity was established over a concentration range of 0.5 to 10,000 μg kg−1 manure with a correlation coefficient ≥0.99. The same experiment was carried out simultaneously with non-labelled SDZ to obtain manure for outdoor soil experiments.
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Acknowledgements
The financial support of the German Research Foundation (DFG) is greatly acknowledged (FOR 566). Many thanks to Bayer AG, Monheim for carrying out the feeding experiments (Dr. J. Köster, Dr. G. Beddies and Dr. C. Corsing) and to A. Lagojda for his support in accurate mass measurements. We thank Jürgen Ebert (Institute of Biology V, RWTH Aachen University) for providing the 13C-labelled SDZ. The authors are grateful to the Ministry of Innovation, Science, Research and Technology of the State of North Rhine-Westphalia for financing a preparative LC system.
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Lamshöft, M., Sukul, P., Zühlke, S. et al. Metabolism of 14C-labelled and non-labelled sulfadiazine after administration to pigs. Anal Bioanal Chem 388, 1733–1745 (2007). https://doi.org/10.1007/s00216-007-1368-y
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DOI: https://doi.org/10.1007/s00216-007-1368-y