Abstract

1. Swertiamarin, a natural ingredient with potent pharmacological activities in the iridoid glycoside family, had been reported to have significant therapeutic effects on a variety of human diseases.

2. In this study, a systematic and efficient strategy based on UHPLC-Q-Exactive Orbitrap mass spectrometry was established to reveal the metabolic profile of swertiamarin in rat urine, plasma, and faeces.

3. First of all, post-acquisition data-mining methods, including multiple mass defect filters (MMDFs) and high-resolution extracted ion chromatograms (HREICs), were developed to screen the metabolite candidates of swertiamarin from the complete mass scan data sets.

4. Second, according to the diagnostic product ions (DPIs), neutral loss fragments (NLFs), chromatographic retention time, accurate mass measurement and calculated Clog P values, all metabolite candidates were rapidly identified.

5. As a consequence, 49 metabolites altogether, including archetype compound, were preliminarily characterised. The corresponding in vivo biotransformation processes, such as dehydration, dehydrogenation, hydroxylation, hydrogenation, methylation, sulphonation, N-acetylcysteine (NAC) formation, N-heterocyclisation and their composite reactions, were all discovered in the study.

6. In conclusion, our results not only detailedly elucidated many new metabolites and metabolic pathways of swertiamarin, but also provided a reference for further study of its pharmacological mechanism and evaluation of its safety.

抽象的

1. 据报道，Swertiamarin是一种在鸢尾糖苷家族中具有强大药理活性的天然成分，对多种人类疾病具有显着的治疗作用。

2. 在这项研究中，建立了基于UHPLC-Q-Exactive Orbitrap质谱分析的系统有效策略，以揭示swertiamarin在大鼠尿液，血浆和粪便中的代谢谱。

3. 首先，开发了包括多质量缺陷过滤器（MMDF）和高分辨率提取离子色谱图（HREIC）在内的采集后数据挖掘方法，以从完整的质量扫描数据集中筛选出swertiamarin的代谢物候选物。

4. 其次，根据诊断产物离子（DPI），中性丢失碎片（NLF），色谱保留时间，准确的质量测量和计算出的Clog P值，可以快速识别所有代谢物。

5. 结果，初步表征了包括原型化合物在内的总共49种代谢物。在研究中发现了相应的体内生物转化过程，如脱水，脱氢，羟基化，氢化，甲基化，磺化，N-乙酰半胱氨酸（NAC）形成，N-杂环化及其复合反应。

6. 综上所述，我们的研究结果不仅详细阐明了swertiamarin的许多新的代谢产物和代谢途径，而且为进一步研究其药理机制和评估其安全性提供了参考。