使用基于质谱的代谢学,通过组装碎片签名,与结构解策略集成,识别异生生物转化产品
Yuan-Chih Chen1, Hsin-Yi Wu2, Wei-Sheng Wu3
1Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
Analytical chemistry
|September 15, 2023
概括
这项研究介绍了FragAssembler,一种新的计算方法,用于准确识别外来生物生物转化产品. 这种方法显著减少了假阳性,提高了毒性和公共卫生监测的可靠性.
科学领域:
- 环境化学环境化学
- 毒理学 毒理学 毒理学
- 计算化学的计算化学
背景情况:
- 准确识别异生物生物转化产品对于评估毒性和致癌性至关重要.
- 由于有限的参考标准和光谱数据,当前的方法通常会产生许多假阳性候选物.
研究的目的:
- 开发和验证一个可靠的战略,可靠地识别出源生物转化产品.
- 为了减少异生菌代谢研究中假阳性结构候选者的数量.
主要方法:
- 利用基于UHPLC-HRMS的代谢学策略,与FragAssembler软件集成,用于阐明代谢物结构.
- 使用质量缺陷过 (MDF) 和初始候选过的多组比较.
- FragAssembler组装了MS/MS光谱签名,以产生生物转化产品的修饰部分.
主要成果:
- 成功确定了24个和13个生物转化产品,分别是二二乙烯基甲酸盐 (DEHP) 和4'-Methoxy-α-pyrrolidinopentiophenone (4-MeO-α-PVP).
- 与BioTransformer 3.0.0相比,FragAssembler将4-MeO-α-PVP生物转化产品候选物的数量减少了大约2.1倍.
- 证明了使用DEHP生物转化产品的方法的可行性和效率.
结论:
- 拟议的UHPLC-HRMS和FragAssembler综合方法提供了一种有效和可靠的方法来识别异生物生物转化产品.
- FragAssembler有效地消除了假阳性反应和结构,在同位素产品上区分了修饰的部分.
- 这一进步对公共卫生监测和毒理学评估具有重大潜力.
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