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首页> 外文期刊>RSC Advances >Nontargeted SWATH acquisition mode for metabolites identification of osthole in rats using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry
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Nontargeted SWATH acquisition mode for metabolites identification of osthole in rats using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry

机译：使用超高效液相色谱-四极杆飞行时间质谱联用的非目标SWATH采集模式用于大鼠骨中代谢产物的鉴定

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Osthole (OST), 7-methoxy-8-isopentenoxycoumarin, is the characteristic constituent found in Cnidium monnieri (L.) Cuss. and possesses excellent pharmacological activities, including anticancer, anti-apoptosis and neuroprotection. In this study, a rapid and reliable method based on ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and MetabolitePilot2.0? software with principal component variable grouping (PCVG) filtering was developed to observe probable metabolites of OST firstly. The high resolution mass data were acquired by data-independent acquisition mode (DIA), i.e. , sequential window acquisition of all theoretical fragmentation spectra (SWATH), which could significantly improved the hit rate of low-level and trace metabolites. A novel data processing method ‘key product ions (KPIs)’ were employed for metabolites rapid hunting and identification as an assistant tool. A total of 72 metabolites of OST were detected in vitro and in vivo , including 39 metabolites in rat liver microsomes (RLMs), 20 metabolites in plasma, 32 metabolites in bile, 32 metabolites in urine and 37 metabolites in feces. The results showed that mono-oxidation, demethylation, dehydrogenation, sulfate conjugation and glucuronide conjugation were major metabolic reactions of OST. More significant, oxydrolysis, 3,4-epoxide-aldehylation, phosphorylation, S -cysteine conjugation and N -acetylcysteine conjugation were considered as unique metabolic pathways of OST, and phosphorylation, S -cysteine conjugation and N -acetylcysteine conjugation reactions were characterized in rat biological samples for the first time. Preparation of active metabolites will be greatly helpful in elucidating the potential biological mechanism of OST, and the proposed metabolic pathways of it might provide further understanding of the safety and efficacy of simple coumarins.
机译：Osthole（OST），即7-甲氧基-8-isopentenoxycoumarin，是在Cnidium monnieri（L.）Cuss中发现的特征性成分。并具有出色的药理活性，包括抗癌，抗凋亡和神经保护作用。在这项研究中，一种基于超高效液相色谱结合四极杆飞行时间质谱（UHPLC-Q-TOF-MS）和MetabolitePilot2.0？的快速可靠的方法。首先开发了具有主成分变量分组（PCVG）过滤功能的软件，以观察OST的可能代谢产物。高分辨率质量数据是通过独立于数据的采集模式（DIA）采集的，即所有理论碎片质谱图（SWATH）的顺序窗口采集，可显着提高低水平和痕量代谢物的命中率。一种新的数据处理方法“关键产物离子（KPI）”被用作代谢物的快速捕集和鉴定辅助工具。在体内和体外共检测到72种OST代谢物，包括大鼠肝微粒体（RLM）中的39种代谢物，血浆中20种代谢物，胆汁中32种代谢物，尿液中32种代谢物和粪便中37种代谢物。结果表明，单氧化，脱甲基，脱氢，硫酸盐结合和葡糖苷酸结合是OST的主要代谢反应。更重要的是，氧解，3,4-环氧-醛化，磷酸化，S-半胱氨酸结合和N-乙酰半胱氨酸结合被认为是OST的独特代谢途径，并且在大鼠中表征了磷酸化，S-半胱氨酸结合和N-乙酰半胱氨酸结合反应。首次生物学样品。活性代谢物的制备将有助于阐明OST的潜在生物学机制，其提议的代谢途径可能提供对简单香豆素的安全性和功效的进一步了解。

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