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基于胺的药物中 NDMA 的形成--预氯化和水基质的影响。

NDMA formation from amine-based pharmaceuticals--impact from prechlorination and water matrix.

机构信息

Department of Civil Engineering, University of Toronto, 35 St. George St., Toronto, Ontario, Canada M5S 1A4.

出版信息

Water Res. 2013 May 1;47(7):2446-57. doi: 10.1016/j.watres.2013.02.017. Epub 2013 Feb 17.

DOI:10.1016/j.watres.2013.02.017
PMID:23453587
Abstract

The presence of N-nitrosodimethylamine (NDMA) in drinking water is most commonly associated with the chloramination of amine-based precursors. One option to control the NDMA formation is to remove the precursors via pre-oxidation, and prechlorination is among the most effective options in reducing NDMA formation. However, most of the findings to-date are based on single-precursor scenarios using the model precursor dimethylamine (DMA) and natural organic matter (NOM), while few studies have considered the potential interactions between water matrix components and the target precursors when investigating the prechlorination impact. Specifically, little is known for the behaviour of amine-based pharmaceuticals which have recently been reported to contribute to NDMA formation upon chloramination. This work demonstrates that prechlorination can affect both the ultimate NDMA conversion and the reaction kinetics from selected pharmaceuticals, and the nature and extent of the impact was compound-specific and matrix-specific. In the absence of NOM, the NDMA formation from most pharmaceuticals was reduced upon prechlorination, except for sumatriptan which showed a consistent increase in NDMA formation with increasing free chlorine contact time. In the presence of NOM, prechlorination was shown to enhance initial reactions by reducing the binding between NOM and pharmaceuticals, but prolonged prechlorination broke down NOM into smaller products which could then form new bonds with pharmaceuticals and thus inhibit their further conversion into NDMA.

摘要

饮用水中 N-亚硝基二甲胺(NDMA)的存在通常与胺基前体的氯化胺化有关。控制 NDMA 形成的一种选择是通过预氧化去除前体,而预氯化是减少 NDMA 形成的最有效方法之一。然而,迄今为止的大多数发现都是基于使用模型前体二甲胺(DMA)和天然有机物(NOM)的单前体情况,而在研究预氯化的影响时,很少有研究考虑水基质成分与目标前体之间的潜在相互作用。具体来说,对于最近报道的在氯化胺化时会导致 NDMA 形成的基于胺的药物的行为知之甚少。这项工作表明,预氯化会影响选定药物的最终 NDMA 转化率和反应动力学,而影响的性质和程度因化合物和基质而异。在没有 NOM 的情况下,大多数药物的 NDMA 形成在预氯化后减少,除了舒马曲坦,它显示出随着自由氯接触时间的增加,NDMA 形成一致增加。在 NOM 存在的情况下,预氯化通过减少 NOM 与药物之间的结合来促进初始反应,但延长的预氯化会将 NOM 分解成更小的产物,这些产物可以与药物形成新的键,从而抑制它们进一步转化为 NDMA。

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