Centre for Ecology and Hydrology-Lancaster, Lancaster Environment Centre, Library Avenue, Bailrigg, Lancaster LA14AP, Lancashire, United Kingdom.
J Chromatogr A. 2011 Nov 25;1218(47):8519-28. doi: 10.1016/j.chroma.2011.09.061. Epub 2011 Sep 29.
A reliable and specific method was developed for the determination of the cytotoxic drugs cyclophosphamide and ifosfamide in sewage effluent. The most successful combination was found to be Strata-X solid-phase extraction followed by Florisil® clean-up with analysis by liquid chromatography-tandem mass spectrometry. Quantification by internal standardisation was achieved using custom synthesised d4-cyclophophosphamide. The mass spectrometer was operated in highly selective reaction monitoring (HSRM) mode, which significantly reduced matrix noise and improved sensitivity. Although it suffered from some ionisation suppression, electrospray ionisation (ESI) was found to give an order of magnitude better sensitivity in terms of limit of detection than atmospheric pressure chemical ionisation (APCI). Using final effluent from two different sewage treatment plants, the method was validated following official European guidelines and shown to be a high performance tool for routine analysis at the sub-nanogram per litre level. Depending on the matrix, the limit of detection for cyclophosphamide was between 0.03 ng/L and 0.12 ng/L and for ifosfamide between 0.05 ng/L and 0.09 ng/L. For cyclophosphamide the accuracy and precision, tested at 1.7 ng/L, were 98-109% and ≤ 13%, CV respectively. For ifosfamide the accuracy and precision, tested at 1.1 ng/L, were 98-113% and ≤ 15% CV, respectively. Depending on the sample matrix the absolute recovery of the internal standard was between 57% and 70%. The method was tested by analysis of spot samples taken from the final effluent discharges of two sewage treatment plants; the first using a conventional trickling filter treatment process and second employing activated sludge followed by ultra violet treatment. Cyclophosphamide was detected at 0.19 ng/L at the first plant and at the second detected at 3.7 ng/L and 3.5 ng/L, before and after the UV treatment process; ifosfamide was not detectable at either plant.
建立了一种可靠且特异的方法，用于测定污水中的细胞毒性药物环磷酰胺和异环磷酰胺。研究发现，固相萃取（Strata-X）与 Florisil®净化的最佳组合，结合液相色谱-串联质谱法进行分析。通过定制合成的 d4-环磷酰胺进行内标定量。质谱仪采用高选择性反应监测（HSRM）模式进行操作，这显著降低了基质噪声并提高了灵敏度。尽管电喷雾电离（ESI）受到一些离子抑制，但与大气压化学电离（APCI）相比，ESI 的检测限灵敏度高出一个数量级。使用来自两个不同污水处理厂的最终出水，按照官方欧洲准则进行方法验证，结果表明该方法是一种用于亚纳克每升水平常规分析的高性能工具。取决于基质，环磷酰胺的检测限在 0.03ng/L 至 0.12ng/L 之间，而异环磷酰胺的检测限在 0.05ng/L 至 0.09ng/L 之间。在 1.7ng/L 时，环磷酰胺的准确度和精密度分别为 98-109%和≤13%CV。在 1.1ng/L 时，异环磷酰胺的准确度和精密度分别为 98-113%和≤15%CV。取决于样品基质，内标的绝对回收率在 57%-70%之间。该方法通过对两个污水处理厂最终出水的点样进行分析进行了测试；第一个采用传统的滴滤处理工艺，第二个采用活性污泥法，然后进行紫外线处理。在第一个工厂检测到 0.19ng/L 的环磷酰胺，在第二个工厂检测到处理前后的 3.7ng/L 和 3.5ng/L 的环磷酰胺；异环磷酰胺在两个工厂都无法检测到。
