Frankenfeld Fabian, Wagmann Lea, Meyer Markus R
Department of Experimental and Clinical Toxicology and Pharmacology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Homburg, Germany.
Drug Test Anal. 2025 Aug;17(8):1336-1343. doi: 10.1002/dta.3839. Epub 2024 Dec 11.
Wastewater (WW)-based epidemiology (WBE) is a powerful tool for screening and surveillance of drugs (of abuse) or new psychoactive substances (NPSs) in larger population. Since the drug market changes frequently, it is crucial for WBE to define screening and surveillance biomarkers considering drug metabolism and (microbial) stability. The aims of the presented work were first to identify metabolites, potentially serving as a WBE biomarker of five deschloroketamine derivatives (DCKDs) in rat feces samples after oral administration in addition to already known urinary metabolites, and second to elucidate the microbial biotransformation and WW stability of five DCKDs and their metabolites detected in urine and feces. Microbial biotransformation and stability of DCKD and their metabolites in WW were assessed by incubating parent compounds at 0.1 mg/L or rat urine or rat feces samples in freshly collected, untreated, influent WW over a period of 24 h. All samples were analyzed using liquid chromatography-high-resolution tandem mass spectrometry. All parent compounds, seven Phase I, and one Phase II metabolite were detected in rat feces samples. After WW incubations, all tested DCKD and their metabolites were still detectable at least in trace amounts, but particularly, peak areas of the Phase II N- and O-glucuronides showed a markable decrease. This is in line with previous findings where Phase II conjugates were identified to be unstable in WW and thus not recommended as a WW biomarker. Hence, incubations demonstrated that the five DCKD and most of their metabolites were sufficiently stable in WW influent and can thus be used as analytical targets in the context of WBE.
基于废水（WW）的流行病学（WBE）是一种用于在更大人群中筛查和监测药物（滥用药物）或新型精神活性物质（NPS）的强大工具。由于药物市场变化频繁，对于WBE来说，考虑药物代谢和（微生物）稳定性来定义筛查和监测生物标志物至关重要。本研究的目的首先是除了已有的尿液代谢物外，确定在大鼠口服给药后粪便样本中可能作为五种去氯氯胺酮衍生物（DCKD）的WBE生物标志物的代谢物，其次是阐明五种DCKD及其在尿液和粪便中检测到的代谢物的微生物生物转化和WW稳定性。通过将母体化合物以0.1mg/L的浓度或大鼠尿液或大鼠粪便样本在新鲜收集的、未经处理的进水WW中孵育24小时，评估DCKD及其代谢物在WW中的微生物生物转化和稳定性。所有样品均使用液相色谱-高分辨率串联质谱进行分析。在大鼠粪便样本中检测到了所有母体化合物、七种I相代谢物和一种II相代谢物。在WW孵育后，所有测试的DCKD及其代谢物至少仍可检测到痕量，但特别是II相N-和O-葡萄糖醛酸苷的峰面积显著下降。这与之前的研究结果一致，即II相结合物在WW中被确定为不稳定，因此不建议作为WW生物标志物。因此，孵育表明五种DCKD及其大多数代谢物在WW进水中具有足够的稳定性，因此可在WBE的背景下用作分析靶点。
