The development of a novel passive water sampler for highly-polar cytotoxic drugs in aquatic systems.

水生系统中药物和个人护理产品的环境发生被认为是一个日益受到关注的领域（Halling-Sorensen et al. 2004）。到目前为止，环境研究的主要重点是中间极性的药物（logkow >1），而不是高极性的化合物（logkow -1到1），如细胞毒性药物（化疗药物）。这些化学物质的本质是防止或破坏细胞增殖，具有胎儿毒性、遗传毒性和致畸性，被认为是河流系统中最危险的污染物（Rowney et al., 2009）。这些化学物质在环境中的出现主要是由于废水处理厂（WWTW）的排放。污水处理过程不能消除这些化学物质，导致微量的化学物质随处理后的废水释放到接收水中。目前没有监管规定来监测环境中的这些化学物质或法定的最大排放水平，尽管这种情况在不久的将来可能会改变。水处理和供应公司，以及监管机构，如环境局，OFWAT和饮用水检验局都意识到这些新出现的化学污染物，并渴望看到一个强大的采样设备与敏感的，可重复的分析方法相结合，以允许常规测量。欧洲医疗机构（EMEA）（许可使用这些药物的机构）提出，单个药物的浓度应为10 ng/L作为环境风险评估的触发值，但在某些情况下，泰晤士河几个取水点的预测环境浓度超过了这个值（Rowney等人，2009年）。本研究的目的是研究一种合适的被动采样矩阵，以便对废水和河水中的这些化学物质进行常规、相对低成本的监测。这些化合物是亲水的（即log Kow ~-1到1），具有高水溶性，对开发被动采样器提出了重大的技术和分析挑战，但完全适合NERC/ACTF学生计划。在兰开斯特大学和CEH科学家组成的专家团队的监督下，这名学生将测试13种最常见的细胞毒性药物的一些聚合吸附剂的适用性。该项目将从检查吸收/净化动力学开始，以确定水生取样率，并将在严格控制的实验室条件下进行。这项工作将与水生降解/转化实验相结合，以检查一系列模拟水类型中的化学行为。将使用基于CEH-Lancaster运行的高分辨率三重四极杆LC-MS/MS系统的分析方法，并且学生将期望建立针对环磷酰胺（常见抗癌药物）开发的初始分析方法。重要的是，英国西北部一家主要的供水/处理公司联合公用事业公司（UU）将作为CASE的合作伙伴，为学生提供额外的培训机会（允许进入他们在沃灵顿的分析实验室），并允许在他们的污水处理厂部署被动采样器。UU将参与该项目的所有阶段，并渴望看到分析方法纳入他们的实验室计划。预计通过部署许多被动采样器在高空间尺度上获得的初步实地数据将随后进行化学命运建模和风险分析。参考文献Halling-Sorensen B， Nielsen SN, Lanzky PF, Ingerslev F, Lutzhoft HCH, Jorgensen SE。1998. 环境中原料药的发生、命运和影响综述。化学环境36:357-394。（~800次引用，2009年11月！）罗尼NC，约翰逊，AC，威廉姆斯，RJ 2009。饮用水中的细胞毒性药物。Env。Toxcol。化学，28:2733

The environmental occurrence of pharmaceuticals and personal care products in aquatic systems is recognized as an area of increasing concern (Halling-Sorensen et al. 2004). To date, the main focus for environmental research has been on pharmaceuticals of intermediate polarity (Log Kow >1) and not on highly polar compounds (Log Kow -1 to 1) such as cytotoxic drugs (chemotherapy agents). These chemicals by their very nature are designed to prevent or disrupt cellular proliferation and have fetotoxic, genotoxic and teratogenic properties and are considered to be the most dangerous contaminants present in river systems (Rowney et al., 2009). The occurrence of these chemicals in the environment occurs primarily due to discharge from waste-water treatment works (WWTW). WWTW processes do not eliminate these chemicals resulting in trace quantities released with treated effluents into receiving waters. There are currently no regulatory requirements to monitor these chemicals in the environment or statutory maximum emission levels, although this is likely to change in the near future. Water treatment and supply companies, as well as regulatory agencies such as the Environment Agency, OFWAT and the Drinking Water Insepctorate are aware of these emerging chemical contaminants and are keen to see a robust sampling device coupled to a sensitive, reproducible analytical method to allow for routine measurements. The European Medical Agency (EMEA) (which licences the use of these drugs) has proposed that concentrations of 10 ng/L for an individual drug should serve as a trigger value for an environmental risk assessment and yet predicted environmental concentrations at several water intake sites on the River Thames exceed this value in some cases (Rowney et al 2009). The purpose of this studentship is to research a suitable passive sampling matrix to enable the routine, relatively low-cost monitoring of these chemicals in effluents and river water. These compounds are hydrophilic (i.e. log Kow ~-1 to 1) with high aqueous solubilities and present a significant technological and analytical challenge for developing a passive sampler but is entirely suitable for the NERC/ACTF studentship programme. The student, under the expert supervision of a team of Lancaster University and CEH scientists, will test the suitability of a number of polymeric sorbents for 13 of the most common cytotoxic drugs. The project will start by examining uptake/depuration kinetics to determine aquatic sampling rates and will be conducted under carefully controlled laboratory conditions. This work will be coupled to aquatic degradation/transformation experiments to examine chemical behaviour in a range of simulated water types. An analytical method, based on a high-resolution triple quadrupole LC-MS/MS system operated at CEH-Lancaster, will be utilised and the student will be expected to build on an initial analytical method developed for cyclophosphamide (common anticancer drug). Importantly, Unitied Utilities (UU), a major water supply/treatement company in the NW of England, will serve as a CASE partner providing additional training opportunities for the student (by allowing access to their analytical laboratory in Warrington) and allowing passive samplers to be deployed at their WWTWs. UU will be involved in all stages of the project and is keen to see the analytical method incorporated into their laboratory programme. It is anticipated that preliminary field data, obtained over a high spatial scale by deploying numerous passive samplers, will then be subject to chemical fate modelling and risk analysis. References Halling-Sorensen B, Nielsen SN, Lanzky PF, Ingerslev F, Lutzhoft HCH, Jorgensen SE. 1998. Occurrence, fate and effects of pharmaceutical substances in the environment - A review. Chemosphere 36: 357-394. (~800 citations, Nov 2009!) Rowney NC, Johnson, AC, Williams, RJ 2009. Cytotoxic drugs in drinking water. Env. Toxcol. & Chemistry. 28:2733