Metabolism of 14C-labelled and non-labelled sulfadiazine after administration to pigs
Metabolism of 14C-labelled and non-labelled sulfadiazine after administration to pigs
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DOI：
10.1007/s00216-007-1368-y
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发表时间：
2007-08-01
影响因子：
4.3
通讯作者：
Spiteller, Michael
中科院分区：
文献类型：
--
作者：
Lamshoeft, Marc;Sukul, Premasis;Spiteller, Michael
通过给育肥猪施用c -14标记兽药，研究磺胺嘧啶（SDZ）及其代谢物的行为。在每天收集粪便后测定其排泄动力学。两种已知的代谢物，n -乙酰磺胺嘧啶和4-羟基磺胺嘧啶，以及两种迄今尚未确定的次要代谢物。使用了各种质谱技术，如母体、产物离子扫描和精确的质量测量。新化合物鉴定为n -甲酰基磺胺嘧啶（For-SDZ）和n -乙酰基-4-羟基磺胺嘧啶（Ac-4-OH-SDZ）。通过合成的真实参考物的光谱和色谱数据的比较，确定了SDZ、Ac-SDZ和For-SDZ的鉴别。羟基化化合物4-OH-SDZ和Ac-4-OH-SDZ用MSn进行了鉴定，并进行了精确的质量测定。10天后，给药的放射性物质只有4%留在猪体内，而SDZ占排出的96%放射性物质的44%。超过93%的标记化合物在粪便中被检测和鉴定。通过先进的测量技术和使用合适的内标，解决了关键的分析问题，即样品提取物中基质的高浓度。各化合物的平均加样回收率为96%。在0.5 ~ 10000 μ g kg（-1）肥料浓度范围内呈线性关系，相关系数>= 0.99。与未标记的SDZ同时进行相同的试验，以获得用于室外土壤试验的肥料。
The behaviour of sulfadiazine (SDZ) and its metabolites was investigated by administering the C-14-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 mu g 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.