Enhanced identification of the in vivo metabolites of Ecliptae Herba in rat plasma by integrating untargeted data-dependent MS2 and predictive multiple reaction monitoring-information dependent acquisition-enhanced product ion scan
| Autor: | Mangmang Sang, Xiumei Gao, Zixin Zhang, Erwei Liu, Lifeng Han, Zhifei Fu, Wenzhi Yang, Mengrong Li, Dandan Si |
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| Rok vydání: | 2019 |
| Předmět: |
Chromatography
Metabolite 010401 analytical chemistry Clinical Biochemistry Selected reaction monitoring Glucuronidation Cell Biology General Medicine Mass spectrometry Wedelolactone 030226 pharmacology & pharmacy 01 natural sciences Biochemistry 0104 chemical sciences Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry In vivo Apigenin Chemical fingerprinting |
| Zdroj: | Journal of Chromatography B. 1109:99-111 |
| ISSN: | 1570-0232 |
| DOI: | 10.1016/j.jchromb.2019.02.001 |
| Popis: | Detection and identification of the in vivo metabolites of traditional Chinese medicine by untargeted profiling strategies are often confronted with severe interference from complex endogenous substances. Here we developed an integral approach, by combining untargeted data-dependent MS2 (dd-MS2) of Q-Orbitrap mass spectrometry and predictive multiple reaction monitoring-information dependent acquisition-enhanced product ion scan (pMRM-IDA-EPI) of triple quadrupole-linear ion trap (QTRAP) mass spectrometry, aiming to detect and identify more extensive metabolites in bio-samples. Ecliptae Herba (EH) is a widely consumed medicinal herb with the effects of nourishing liver/kidney, but its metabolites in vivo have not been fully elucidated. Firstly, after UHPLC separation on an HSS T3 column, chemical fingerprinting of 70% ethanolic extract of EH was performed by untargeted dd-MS2 in negative ion mode. We could characterize 41 compounds from EH, and 24 were detectable in the plasma of rats (prototypes) after oral administration of EH extract (1 g/kg). Secondly, using echinocystic acid (triterpene), wedelolactone (coumarin), and apigenin (flavonoid) as the different parent templates, an MRM list containing 150 predicted ion-pairs was established to enhance MS2 scan by pMRM-IDA-EPI, which enabled the primary identification of up to 200 metabolites. The biotransformations mainly involve oxidation, hydrogenation, methylation, glucuronidation, sulfonation etc. Thirdly, the rat plasma samples obtained after oral administration of three pure compounds (echinocystic acid, wedelolactone and apigenin) were analyzed to verify the reliability of metabolites identification, and 11, 4, and 10 metabolites were found individually. This is the first comprehensive research on the metabolism of EH in vivo. |
| Databáze: | OpenAIRE |
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