Abstract
Levophencynonate is an anticholinergic agent which can prevent acute motion sickness with an efficacy similar to scopolamine. It will take effect by competitive binding to central muscarinic acetylcholine receptors. Previously, there was only one investigation about metabolites of phencynonate in rats and ten metabolites have been found. A HPLC/Triple TOF MS method was established and successfully applied to investigate the in vivo metabolites of levophencynonate after a 2 mg levophencynonate hydrochloride tablet was administrated to healthy volunteers. A total of 13 metabolites were found in human specimens, including six from plasma and all of 13 from urine. The metabolites consisted of phase I and phase II products, including demethylation (M1), demethylation/oxidation (M2, M3, M4, and M5), demethylation/methylene to ketone (M6, M7), oxidation (M8, M9), desaturation (M10), demethylation/desaturation (M11), di-oxidation (M12), and oxidation/glucuronidation (M13) metabolites. Products of demethylation (M1), demethylation/desaturation (M11), and oxidation/glucuronidation (M13) were the main metabolites with higher intensity than the others. These findings would provide an important basis for the clinical application and further study of levophencynonate. In addition to the feasibility of the HPLC/Triple TOF MS approach for rapid and reliable characterization of metabolites, the identifications of precise structures of these metabolites need to be confirmed by other techniques, such as 1H and 13C NMR, and in order to elucidate a more detailed metabolic profile of levophencynonate.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Beijing Hospital (Beijing, China) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The approval notice number of this research was 2013BJYYEC-050-02. In this study, a total of ten healthy volunteers were enrolled after signing the Informed Consent Forms.
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Li, B., Shi, A., Si, D. et al. Identification of In Vivo Metabolites of Levophencynonate in Human Plasma and Urine by High-Performance Liquid Chromatography Tandem Triple-Time-of-Flight Mass Spectrometry. Chromatographia 80, 417–426 (2017). https://doi.org/10.1007/s10337-017-3264-8
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DOI: https://doi.org/10.1007/s10337-017-3264-8