A high‐resolution mass spectrometric approach to a qualitative and quantitative comparative metabolism of the humantenine‐type alkaloid rankinidine

التفاصيل البيبلوغرافية
العنوان: A high‐resolution mass spectrometric approach to a qualitative and quantitative comparative metabolism of the humantenine‐type alkaloid rankinidine
المؤلفون: Meng‐Die Gong, Jiao‐Yan Qin, Meng‐Ting Zuo, Xue‐Jia Qi, Yong Wu, Xiao‐Feng Zheng, Zhao‐Ying Liu
المصدر: Rapid Communications in Mass Spectrometry. 36
بيانات النشر: Wiley, 2022.
سنة النشر: 2022
مصطلحات موضوعية: Alkaloids, Indoles, Swine, Tandem Mass Spectrometry, Organic Chemistry, Microsomes, Liver, Animals, Antineoplastic Agents, Chromatography, High Pressure Liquid, Gelsemium, Spectroscopy, Rats, Analytical Chemistry
الوصف: Rankinidine belongs to the humantenine-type alkaloids isolated from Gelsemium. Currently, the mechanism behind the toxicity differences of rankinidine has not been explained. In this study, our purpose was to elucidate the major in vitro metabolic pathways of rankinidine and to compare the formation of metabolites of rankinidine in human (HLMs), rat (RLMs), goat (GLMs) and pig (PLMs) liver microsomes.This is the first study to compare the in vitro metabolism of rankinidine with high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/QTOF). The MS/MS data and LC/MS peak area acquired in positive ion mode were used to analyze metabolite structures and compare metabolism.We identified 11 metabolites (M1-M11) in total and found five main metabolic pathways, consisting of demethylation (M1), reduction (M2), oxidation at different positions (M3-M5), oxidation and reduction (M6-M10) and demethylation and oxidation (M11). The metabolism of rankinidine has qualitative and quantitative species-specific differences in vitro. In PLMs and GLMs, the main metabolic pathway of rankinidine was oxidation. Notably, among the four species, the oxidation ability of rankinidine was highest in pigs and goats, and the demethylation and reduction abilities of rankinidine were highest in humans and rats.The interspecific metabolic differences of rankinidine in HLMs, PLMs, GLMs and RLMs were compared and studied for the first time using LC/QTOF. These findings will certainly support future studies of rankinidine metabolism in vivo and will contribute to elucidating the cause of species-specific differences behind Gelsemium toxicity.
تدمد: 1097-0231
0951-4198
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::02ffe52f5de6b389f8936ddbb5ecb1df
https://doi.org/10.1002/rcm.9302
حقوق: CLOSED
رقم الأكسشن: edsair.doi.dedup.....02ffe52f5de6b389f8936ddbb5ecb1df
قاعدة البيانات: OpenAIRE