超高效液相色谱-串联质谱法研究氯氟醚菌唑在斑马鱼体内的对映选择性富集代谢  

Study on Enantioselective Enrichment Metabolism of Mefentrifluconazole in Zebrafish by Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry

作　　者：张苹 孙晓芳 钟言茹 孔令茹 吴琦琦 施海燕[1] 王鸣华[1] ZHANG Ping;SUN Xiao-Fang;ZHONG Yan-Ru;KONG Ling-Ru;WU Qi-Qi;SHI Hai-Yan;WANG Ming-Hua(College of Plant Protection,Nanjing Agricultural University,Nanjing 210095,China)

机构地区：[1]南京农业大学植物保护学院,南京210095

出　　处：《分析化学》2023年第10期1632-1650,共19页Chinese Journal of Analytical Chemistry

基　　金：国家重点研发计划项目(No.2021YFD1700104)资助

摘　　要：为阐明氯氟醚菌唑对水生生物斑马鱼的对映体选择性生物效应及其对生态环境和人类健康的影响,本研究在开展斑马鱼96 h急性毒性实验的基础上,研究了氯氟醚菌唑在斑马鱼体内的对映体选择性富集代谢行为,同时利用高分辨质谱鉴定了氯氟醚菌唑在斑马鱼体内的代谢产物,并进一步推断了其主要代谢途径。结果表明,氯氟醚菌唑对斑马鱼为中等毒性,毒性顺序为S-氯氟醚菌唑>Rac-氯氟醚菌唑>R-氯氟醚菌唑,S-氯氟醚菌唑毒性分别为R-和Rac-氯氟醚菌唑的2.0和1.4倍。氯氟醚菌唑在斑马鱼体内存在对映选择性富集和代谢行为,表现为R-氯氟醚菌唑优先被富集而在低浓度处理组中优先被代谢。同时,鉴定了氯氟醚菌唑在斑马鱼体内的8种代谢产物,推测其主要代谢途径为通过羟基化反应生成Ⅰ相代谢物,进而在磺基转移酶和葡萄糖醛酸糖基转移酶的作用下生成硫酸酯化合物和葡萄糖醛酸络合物。本研究首次在斑马鱼体内鉴定出了羟基化代谢物M074和葡萄糖醛酸络合物M035、M045以及硫酸酯化合物M057、M071。A method for investigation of enantioselective biological effects of chiral fungicide mefentrifluconazole on zebrafish to provide reference for assessment of biosafety and human health risks in aquatic environment by ultra-high performance liquid chromatography-tandem mass spectrometry was developed in this study.On the basis of acute toxicity test for 96 h,the enantioselective uptake-metabolism,metabolites and metabolic pathways of mefentrifluconazole in zebrafish were investigated by high resolution mass spectrometry.The results showed that mefentrifluconazole was moderately toxic to zebrafish,and the toxicity order was S-mefentrifluconazole>Racmefentrifluconazole>R-mefentrifluconazole.Among which,S-mefentrifluconazole was 2.0 and 1.4 times more toxic than R-and Rac-mefentrifluconazole,respectively.The enantioselective uptake-metabolism behavior in zebrafish manifested that R-mefentrifluconazole was preferentially enriched and metabolized in low-concentration treatment group.Finally,eight metabolites of mefentrifluconazole in zebrafish were identified.It was speculated that the main metabolic pathway was the formation of phaseⅠmetabolites through hydroxylation reaction,and then the formation of sulfate compounds and glucuronic acid complexes under the action of sulfotransferase and glucuronic acid glucuronase.The hydroxylated metabolite M074 and the glucuronide complexes M035 and M045,as well as the sulfate compounds M057 and M071,were identified for the first time in zebrafish.

关 键 词：氯氟醚菌唑 超高效液相色谱-串联质谱 对映选择性 斑马鱼 富集代谢 

分 类 号：O657.63[理学—分析化学] TS254.7[理学—化学]