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A high-resolution mass spectrometric approach to a qualitative and quantitative comparative metabolism of the humantenine-type alkaloid rankinidine. | LitMetric

AI Article Synopsis

  • Rankinidine, a toxic alkaloid from Gelsemium, has unexplained differences in toxicity, prompting a study to explore its metabolic pathways across different species, including humans and animals.
  • The research utilized high-performance liquid chromatography and mass spectrometry to identify 11 metabolites and five main metabolic pathways, revealing species-specific variations in rankinidine metabolism.
  • Findings indicated that pigs and goats primarily metabolize rankinidine through oxidation, while humans and rats excel in demethylation and reduction, providing insights for future studies on Gelsemium toxicity.

Article Abstract

Rationale: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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Source
http://dx.doi.org/10.1002/rcm.9302DOI Listing

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