LC-MS/MS method for the determination of melamine in rat plasma: toxicokinetic study in Sprague-Dawley rats.
LC-MS/MS method for the determination of melamine in rat plasma: toxicokinetic study in Sprague-Dawley rats.
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DOI：
10.1002/jssc.200900201
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发表时间：
2009-09
影响因子：
3.1
通讯作者：
Feng Yang;Y. Mao;Xiaodong Zhang;Zhiqiang Ma;Xinrong Zhang
中科院分区：
文献类型：
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作者：
Feng Yang;Y. Mao;Xiaodong Zhang;Zhiqiang Ma;Xinrong Zhang
最近，三聚氰胺引起了国际社会的关注，因为受污染的婴儿配方奶粉对其健康造成了灾难性的影响。到目前为止，关于三聚氰胺在哺乳动物体内的药代动力学信息有限。建立了一种灵敏的三聚氰胺在大鼠体内药代动力学研究的高效液相-电喷雾质谱质谱联用方法。该方法采用简单的液-液萃取法净化血浆样品，不同浓度三聚氰胺的萃取回收率一致。三聚氰胺血药浓度在10~5000 ng/m L范围内与色谱峰面积呈良好的线性关系(R=0.995)。在这项工作中，首次将三聚氰胺静脉和口服给SD大鼠，并研究了该污染物的药代动力学特征。三聚氰胺在SD大鼠体内的主要药代动力学参数、平均稳态分布体积(V(Ss))、清除量和血浆消除半衰期(T(1/2))的平均值分别为72.9±13.2%、102.5±-12.5m L/kg、2 0.1±-3.8m L/h/kg和4.9±-0.5h。大鼠药代动力学研究结果表明，三聚氰胺主要局限于血液或细胞外液，并未广泛分布于大多数器官组织。同时，三聚氰胺应该主要通过大鼠的肾脏过滤来消除，不会发生明显的代谢。这些数据应该有助于监管机构进行风险评估。
Most recently, melamine has raised international concern for its catastrophic health effects stemming from tainted infant formula. So far there is limited information concerning the pharmacokinetics of melamine in mammals. The present report concerns the development and validation of a sensitive HPLC-ESI-MS/MS method for the pharmacokinetic study of melamine in rat. The method employed a simple liquid-liquid extraction process for plasma sample cleanup, and the extraction recoveries of melamine from plasma were consistent at different concentrations. There was a linear relationship between chromatographic area and concentration over the range of 10-5000 ng/mL for melamine in plasma (R = 0.995). In this work, for the first time, melamine was administered intravenously and orally to Sprague-Dawley rats and the pharmacokinetic characteristics of this contaminant were investigated. The mean values of major pharmacokinetic parameters of oral availability, the mean steady-state distribution volume (V(ss)), clearance, and plasma elimination half-life (T(1/2)) of melamine in Sprague-Dawley rats were 72.9 +/- 13.2%, 102.5 +/- 12.5 mL/kg, 20.1 +/- 3.8 mL/h/kg, and 4.9 +/- 0.5 h, respectively. The rats pharmacokinetic study results suggested that melamine was predominantly restricted to blood or extracellular fluid and is not extensively distributed to most organ tissues. Meanwhile, melamine should be primarily eliminated by renal filtration for rats and does not undergo significant metabolism. These data should be useful to regulatory for risk assessment.