Low biodegradability of fluoxetine HCl, diazepam and their human metabolites in sewage sludge-amended soil
Low biodegradability of fluoxetine HCl, diazepam and their human metabolites in sewage sludge-amended soil
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DOI：
10.1007/s11368-008-0024-2
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发表时间：
2008-09-01
影响因子：
3.6
通讯作者：
Rowland, Steven J.
中科院分区：
文献类型：
--
作者：
Redshaw, Clare H.;Cooke, Martin P.;Rowland, Steven J.
背景、目标和范围 欧盟于 1998 年禁止在欧洲进行海上污水污泥 (SS) 处置。自那时起，SS 的陆地应用率显着上升，并将进一步上升。 2000 年，52% 的 SS 被处置到英国的土地上。因此，土地应用可能是与 SS 相关的有机化学品进入环境的重要运输途径。目前欧盟正在使用 3,000 多种不同的药物成分，其中许多成分进入污水系统。可能的结果是，过去十年关于环境中（例如水道、公海和土壤）中药理活性化合物的报告有所增加。令人惊讶的是，对于药物在环境中，特别是在土壤中的运输和归宿仍然严重缺乏了解。因此，本项目研究了来自英国 SS 改良土壤的短期（60 天）细菌液体培养物中选择性血清素再摄取抑制剂百忧解（R）（盐酸氟西汀）和 1,4-苯二氮卓类药物安定（R）（地西泮）及其主要人体代谢物（盐酸诺氟西汀、替马西泮和奥沙西泮）对微生物降解的敏感性。方法学 最近开发的提取技术，包括固相萃取，可以从生物降解培养物（水和土壤基质）中分离出所有分析物，随后使用新型高效液相色谱-电喷雾电离-多级质谱 (HPLC-ESI-MSn) 技术进行分析。使用氘代内标进行比率校准可以生成定量数据。还进行了简单的碱化互变异构实验以帮助鉴定细菌转化产物。除了生物降解研究之外，细菌藿烷多元醇（BHP；细菌膜标记化学品）的 HPLC-APCI-MSn 分析可以评估 SS 改良土壤中的微生物群落结构。结果 在液体培养研究（60 天）中发现药物具有抗生物降解性，甚至在长期暴露于 SS 改良土壤中（> 200 天；仅盐酸氟西汀）后也是如此。奥沙西泮是唯一一种在液体培养研究中经历生物转化（约 40%）的 1,4-苯二氮卓类药物。提出了支持转化产物是 1,4-苯二氮卓互变异构体这一理论的证据。八种不同的 SS 改良土壤的 BHP 分布表明，在这些生物降解研究中用作培养源的土壤的受限细菌群落是 SS 改良土壤的典型特征。讨论 在模拟但真实的 SS 改良土壤条件下，除奥沙西泮外的所有目标分析物均未发生实质性降解，这表明它们可能具有持久性。尽管奥沙西泮确实经历了显着的生物（和非生物）损失，但在生物影响下形成的代谢物被假设为另一种具有生物活性的1,4-苯二氮卓类药物（2-烯醇或3-烯醇去甲地西泮），其可能对进一步的变化具有抵抗力。 SS 改良土壤中的细菌群落可能无法降解此类化合物。建议和观点 对于此处测试的此类药物，有可能在田间土壤等环境中积累，SS 定期添加到田间土壤中，作为处置机制和肥料。当化合物积累时，迁移到其他环境成分的风险就变得更大。对于田间土壤，这些可能包括对动植物的潜在接触以及可能的生物累积或对陆地生物的影响以及植物中的累积，包括在 SS 处理的土壤上生长的作物。许多药物在陆地环境中的命运和后续影响仍然很大程度上未知，需要进一步研究才能充分评估与 SS 相关的药物的风险（如果有）。
Background, aim, and scope The European Union banned disposal of sewage sludge (SS) at sea in Europe in 1998. Since that time, the application rate of SS to land has risen significantly and is set to rise further. Fifty-two percent of SS was disposed to land in the UK in 2000. Land application is, thus, possibly an important transport route for SS-associated organic chemicals into the environment. There are now over 3,000 different pharmaceutical ingredients in use in the EU and many enter sewage systems. Possibly as a result, the last decade has seen an increase in reports of pharmacologically active compounds in the environment (e. g. in watercourses, open ocean and soils). Surprisingly, there is still a significant lack of knowledge of the transport and fate of pharmaceuticals in the environment, particularly in soils. The present project, therefore, investigated the susceptibility to microbial degradation of the selective serotonin re-uptake inhibitor, Prozac(R) (fluoxetine HCl), and the 1,4-benzodiazepine, Valium(R) (Diazepam) and their major human metabolites (norfluoxetine HCl, temazepam and oxazepam) in short-term (60 day) bacterial liquid cultures derived from UK SS-amended soil and of fluoxetine HCl in a longer-term (270 day) SS-amended soil culture.Methodology Recently developed extraction techniques, including solid phase extraction, allowed all analytes to be isolated from the biodegradation cultures (aqueous and soil matrices), and subsequently analysed using novel high performance liquid chromatography-electrospray ionization-multistage mass spectrometry (HPLC-ESI-MSn) techniques. Ratio calibration using deuterated internal standards allowed the generation of quantitative data. A simple basified tautomerism experiment was also performed to aid in the identification of a bacterial transformation product. Alongside the biodegradation studies, HPLC-APCI-MSn profiling of bacteriohopanepolyols (BHPs; bacterial membrane marker chemicals) allowed assessment of the microbial community structure in the SS-amended soils.Results The pharmaceuticals were found to be resistant to biodegradation in liquid culture studies (60 days), and even after prolonged exposure in SS-amended soil (> 200 days; fluoxetine HCl only). Oxazepam was the only 1,4-benzodiazepine studied which underwent biotic transformation (similar to 40%) in liquid culture studies. Evidence to support the theory that the transformation product was a 1,4-benzodiazepine tautomer, is presented. BHP profiles of eight different SS-amended soils suggested that the restricted bacterial community of the soil used as a culture source in these biodegradation studies was typical of SS-amended soils.Discussion The lack of substantial degradation of all target analytes except oxazepam under simulated, but realistic, SS-amended soil conditions indicates their likely persistent nature. Although oxazepam did undergo significant biotic (and abiotic) losses, the metabolite formed under biotic influences was hypothesised to be another bioactive 1,4-benzodiazepine (either 2-enol or 3-enol nordiazepam) which is likely to be resistant to further change. The bacterial communities in SS-amended soils may be unable to degrade such compounds.Recommendations and perspectives With such pharmaceuticals as tested here, there is a potential for accumulation within environments such as field soil to which SS is regularly added both as a disposal mechanism and as a fertiliser. When compounds undergo accumulation, the risk of transport to other environmental components becomes more likely. From field soils, these may include potential exposure to flora and fauna and possible bioaccumulation or effects on terrestrial organisms and accumulation in plants, including crops grown on the SS-treated soils. The fate and subsequent impact of many pharmaceuticals within the terrestrial environment is still largely unknown and further research is required before the risks, if any, of SS-associated pharmaceuticals can be fully assessed.