Jožef Stefan Institute, Jamova cesta 39, 1000, Ljubljana, Slovenia.
Jožef Stefan International Postgraduate School, Jamova cesta 39, 1000, Ljubljana, Slovenia.
Environ Sci Pollut Res Int. 2016 Jun;23(11):11209-11223. doi: 10.1007/s11356-016-6321-1. Epub 2016 Feb 27.
This study describes a gas chromatography-mass spectrometry analytical method for the analysis of cytostatic cyclophosphamide (CP), ifosfamide (IF) and their selected metabolites/transformation products (TPs): carboxy-cyclophosphamide (carboxy-CP), keto-cyclophosphamide (keto-CP) and 3-dechloroethyl-ifosfamide/N-dechloroethyl-cyclophosphamide (N-decl-CP) in wastewater (WW). Keto-cyclophosphamide, CP and IF were extracted with Oasis HLB and N-decl-CP and carboxy-CP with Isolute ENV+ cartridges. Analyte derivatization was performed by silylation (metabolites/TPs) and acetylation (CP and IF). The recoveries and LOQs of the developed method were 58, 87 and 103 % and 77.7, 43.7 and 6.7 ng L(-1) for carboxy-CP, keto-CP and N-decl-CP, respectively. After validation, the analytical method was applied to hospital WW and influent and effluent samples of a receiving WW treatment plant. In hospital WW, levels up to 2690, 47.0, 13,200, 2100 and 178 ng L(-1) were detected for CP, IF, carboxy-CP, N-decl-CP and keto-CP, respectively, while in influent and effluent samples concentrations were below LOQs. The formation of TPs during abiotic treatments was also studied. Liquid chromatography-high-resolution mass spectrometry was used to identify CP and IF TPs in ultrapure water, treated with UV and UV/H2O2. UV treatment produced four CP TPs and four IF TPs, while UV/H2O2 resulted in five CPs and four IF TPs. Besides already known TPs, three novel TPs (CP-TP138a, imino-ifosfamide and IF-TP138) have been tentatively identified. In hospital WW treated by UV/O3/H2O2, none of the target metabolites/TPs resulted above LOQs.
本研究描述了一种用于分析细胞毒性环磷酰胺（CP）、异环磷酰胺（IF）及其选定代谢物/转化产物（TPs）的气相色谱-质谱分析方法：羧基-环磷酰胺（carboxy-CP）、酮-环磷酰胺（keto-CP）和 3-去氯乙基-异环磷酰胺/N-去氯乙基-环磷酰胺（N-decl-CP）在废水中（WW）。酮-环磷酰胺、CP 和 IF 用 Oasis HLB 提取，N-decl-CP 和 carboxy-CP 用 Isolute ENV+ 提取。通过硅烷化（代谢物/TPs）和乙酰化（CP 和 IF）对分析物进行衍生化。该方法的回收率和 LOQs 分别为 58%、87%和 103%，以及 77.7、43.7 和 6.7ng/L 用于 carboxy-CP、keto-CP 和 N-decl-CP。经过验证，该分析方法应用于医院 WW 以及接收 WW 处理厂的进水和出水样品。在医院 WW 中，检测到 CP、IF、carboxy-CP、N-decl-CP 和 keto-CP 的浓度分别高达 2690、47.0、13200、2100 和 178ng/L，而进水和出水样品的浓度均低于 LOQs。还研究了在非生物处理过程中 TPs 的形成。使用液相色谱-高分辨率质谱法在超纯水中鉴定 CP 和 IF 的 TPs，并用 UV 和 UV/H2O2 处理。UV 处理产生了四种 CP TPs 和四种 IF TPs，而 UV/H2O2 则产生了五种 CP 和四种 IF TPs。除了已知的 TPs 外，还初步鉴定了三种新型 TPs（CP-TP138a、亚氨基异环磷酰胺和 IF-TP138）。在经 UV/O3/H2O2 处理的医院 WW 中，没有一种目标代谢物/TPs 的浓度超过 LOQs。
