Yang Feng, Mao Yu, Zhang Xiaodong, Ma Zhiqiang, Zhang Xinrong
College of Pharmacy, Department of Chemistry, Second Military Medical University, Shanghai, China.
J Sep Sci. 2009 Sep;32(17):2974-8. doi: 10.1002/jssc.200900201.
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.
最近，三聚氰胺因其对受污染婴儿配方奶粉所产生的灾难性健康影响而引发了国际关注。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。本报告涉及一种灵敏的高效液相色谱-电喷雾串联质谱法（HPLC-ESI-MS/MS）的开发与验证，用于大鼠体内三聚氰胺的药代动力学研究。该方法采用简单的液-液萃取过程对血浆样品进行净化，三聚氰胺从血浆中的萃取回收率在不同浓度下保持一致。血浆中三聚氰胺浓度在10 - 5000 ng/mL范围内时，色谱峰面积与浓度呈线性关系（R = 0.995）。在本研究中，首次对Sprague-Dawley大鼠静脉注射和口服三聚氰胺，并研究了这种污染物的药代动力学特征。Sprague-Dawley大鼠中三聚氰胺的口服生物利用度、平均稳态分布容积（V(ss)）、清除率和血浆消除半衰期（T(1/2)）等主要药代动力学参数的平均值分别为72.9 ± 13.2%、102.5 ± 12.5 mL/kg、20.1 ± 3.8 mL/h/kg和4.9 ± 0.5 h。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，并未广泛分布到大多数器官组织。同时，对于大鼠而言，三聚氰胺主要通过肾滤过消除，且不发生显著代谢。这些数据对监管机构进行风险评估应具有参考价值。
