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Zhao-ying Liu - One of the best experts on this subject based on the ideXlab platform.
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Characterization of absorbed and produced constituents in goat plasma urine and faeces from the herbal medicine Gelsemium elegans by using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.
Journal of ethnopharmacology, 2020Co-Authors: Meng-ting Zuo, Zi-yuan Wang, Kun Yang, Chong-ying Huang, Yan-chun Liu, Xue-jiao Zhao, Zhao-ying LiuAbstract:Abstract Ethnopharmacological relevance Herbal medicine contains hundreds of natural products, and studying their absorption, metabolism, distribution, and elimination presents great challenges. Gelsemium elegans (G. elegans) is a flowering plants in the Loganiaceae family. The plant is known to be toxic and has been used for many years as a traditional Chinese herbal medicine for the treatment of rheumatoid arthritis, neuropathic pain, spasticity, skin ulcers and cancer. It was also used as veterinary drugs for deworming, promoting animal growth, and pesticides. At present, studies on the metabolism of G. elegans have primarily focused on only a few single available reference ingredients, such as koumine, Gelsemine and gelsedine. Material and methods The goal of this work is to elucidate the overall metabolism of whole G. elegans powder in goats using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS). Results Analyses of plasma, urine and fecal samples identified or tentatively characterized a total of 44 absorbed natural products and 27 related produced metabolites. Gelsedine-type, sarpagine-type and Gelsemine-type alkaloids were the compounds with the highest metabolite formation. In the present study, most natural products identified in G. elegans were metabolized through glucuronidation and oxidation. Hydrogenation, dehydrogenation and demethylation also occurred. Conclusion To our knowledge, this is the first report of the metabolite profiling of the G. elegans crude extract in goats, which is of great significance for a safer and more rational application of this herbal medicine.
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The Metabolism and Disposition of Koumine, Gelsemine and Humantenmine from Gelsemium.
Current drug metabolism, 2019Co-Authors: Zi-yuan Wang, Meng-ting Zuo, Zhao-ying LiuAbstract:Background Gelsemium is a toxic flowering plant of the Gelsemiaceae family. It is used to treat skin diseases in China, and it is an important medicinal and homeopathic plant in North America. Up to now, more than 200 compounds have been isolated and reported from Gelsemium. More than 120 of these are indole alkaloids, including the main components, koumine, Gelsemine and humantenmine which produce the pharmacological and toxicological effects of Gelsemium. However, their clinical application their limited by its narrow therapeutic window. Therefore, it is very important to study the metabolism and disposition of indole alkaloids from Gelsemium before their clinical application. This paper reviews all the reports on the metabolism and disposition of alkaloids isolated from Gelsemium at home and abroad. Methods The metabolism and disposition of alkaloids from Gelsemium were searched by the Web of Science, NCBI, PubMed and some Chinese literature databases. Results Only koumine, Gelsemine and humantenmine have been reported, and few other alkaloids have been described. These studies indicated that the three indole alkaloids are absorbed rapidly, widely distributed in tissues, extensively metabolized and rapidly eliminated. There are species differences in the metabolism of these alkaloids, which is the reason for the differences in their toxicity in animals and humans. Conclusion This review not only explains the pharmacokinetics of indole alkaloids from Gelsemium but also facilitates further study on their metabolism and mechanism of toxicity.
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The Difference in Cytotoxic Activity between Two Optical Isomers of Gelsemine from Gelsemium elegans Benth. on PC12 Cells
Molecules (Basel Switzerland), 2019Co-Authors: Li Lin, Yan-chun Liu, Zhao-ying LiuAbstract:Two optical isomers, +/− Gelsemine (1, 2), together with one known compound were isolated from the whole plant of G. elegans. The structures of the separated constituents were elucidated on 1D and 2D (1H-1H COSY, HMBC, HSQC) NMR spectroscopy and high-resolution mass spectrometry (HRMS). The isolated alkaloids were tested in vitro for cytotoxic potential against PC12 cells by the MTT assay. As a result, (+) Gelsemine (compound 1) exhibited cytotoxic activity against PC12 cells with an IC50 value of 31.59 μM, while (−) Gelsemine (compound 2) was not cytotoxic.
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Development and in-house validation of a sensitive LC-MS/MS method for simultaneous quantification of Gelsemine, koumine and humantenmine in porcine plasma.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2018Co-Authors: Kun Yang, Yan-chun Liu, Zhi-liang Sun, Xue-ming Long, Fu-hua Chen, Xiao-feng Liu, Zhao-ying LiuAbstract:Abstract Three monomers of G. elegans indole alkaloids (Gelsemine, koumine and humantenmine) were simultaneously detected in porcine plasma for the first time with the development and validation of a sensitive and reliable LC-ESI-MS/MS method. Using a gradient mobile phase at a constant flow rate of 0.2 mL/min via electrospray ionization (positive ion mode) in a multiple reaction monitoring (MRM) scan, Gelsemine, koumine and humantenmine were eluted, separated and detected at an appropriate retention time. The porcine plasma was prepared using protein precipitation with 1% formic acid-acetonitrile: methanol (2:1, v/v). Using matrix-matched calibration curves and weighted least squares linear regression, a good linearity (r2 > 0.99) was achieved with a concentration range of 0.1–200 μg/L for Gelsemine, koumine and humantenmine; estimated LOD and LOQ values were 0.10 μg/L and 0.2 μg/L, respectively. The mean of the recoveries was in the range of 82.68–100.35% of porcine plasma at four different levels, and the intra-day and inter-day precision (CV) were lower than 15% with a range of 2.46–8.76% and 2.73–10.83%, respectively. The proposed method has proved to be suitable for accurate, quantitative determination of Gelsemine, koumine and humantenmine in porcine plasma.
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identification of Gelsemine metabolites in rat liver s9 by high performance liquid chromatography quadrupole time of flight mass spectrometry
Rapid Communications in Mass Spectrometry, 2018Co-Authors: Kun Yang, Yan-chun Liu, Ya-jun Huang, Zhi-liang Sun, Yi-song Liu, Qi Tang, Sa Xiao, Zhao-ying LiuAbstract:Rationale Gelsemine has been extensively studied because of its anti-tumor, immunomodulatory, insecticidal itching and other significant effect. However, limited information on the pharmacokinetics and metabolism of Gelsemine has been reported. Therefore, the purpose of the present study was to investigate the in vitro metabolism of Gelsemine in rat liver S9 by using a rapid and accurate high-performance liquid chromatography/ quadrupole-time-of-flight mass spectrometry (HPLC/QqTOF-MS). Methods The incubation mixture was processed with 15% trichloroacetic acid. Multiple scans of Gelsemine metabolites and accurate mass measurements were automatically performed simultaneously through data-dependent acquisition in only a 30-min analysis. The structural elucidations of these metabolites were performed by comparing their changes in accurate molecular masses and product ions with those of the parent drug. Results Five metabolites of Gelsemine were identified in rat liver S9. Among of these, four metabolites of Gelsemine were identified for the first time. The present results showed that the metabolic pathways of Gelsemine are oxidation, demethylation, and dehydrogenation in rat liver S9. Conclusions In this study, metabolites of Gelsemine in liver S9 were identified and elucidated firstly using HPLC/QqTOF-MS method. The proposed metabolic pathways of Gelsemine in liver S9 will provide a basis for further studies of the in vivo metabolism of Gelsemine in animals and humans.
Matthew J. Sharp - One of the best experts on this subject based on the ideXlab platform.
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Aza-Cope Rearrangement-Mannich Cyclizations for the Formation of Complex Tricyclic Amines: Stereocontrolled Total Synthesis of (±)-Gelsemine
Journal of the American Chemical Society, 2005Co-Authors: William G. Earley, Jon E. Jacobsen, Andrew Madin, G. Patrick Meier, Christopher J. O'donnell, David W. Old, Larry E. Overman, Matthew J. SharpAbstract:A detailed examination of the use of aza-Cope rearrangement−Mannich cyclization sequences for assembling the azatricyclo[4.4.0.02,8]decane core of Gelsemine is described. Iminium ions and N-acyloxyiminium ions derived from endo-oriented 1-methoxy- or 1-hydroxybicyclo[2.2.2]oct-5-enylamines do not undergo the first step of this sequence, cationic aza-Cope rearrangement, to form cis-hydroisoquinolinium ions. However, the analogous base-promoted oxy-aza-Cope rearrangement does take place to form cis-hydroisoquinolones containing functionality that allows iminium ions or N-acyloxyiminium ions to be generated regioselectively in a subsequent step. Mannich cyclization of cis-hydroisoquinolones prepared in this way efficiently assembles the azatricyclo[4.4.0.02,8]decane unit of Gelsemine. Using a sequential base-promoted oxy-aza-Cope rearrangement/Mannich cyclization sequence, gram quantities of azatricyclo[4.4.0.02,8]decanone 18, a central intermediate in our total of (±)-Gelsemine, were prepared from 3-methyla...
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Use of the Intramolecular Heck Reaction for Forming Congested Quaternary Carbon Stereocenters. Stereocontrolled Total Synthesis of (±)-Gelsemine
Journal of the American Chemical Society, 2005Co-Authors: Andrew Madin, Christopher J. O'donnell, David W. Old, Larry E. Overman, Matthew J. SharpAbstract:Intramolecular Heck reactions of α,β-unsaturated 2-haloanilides derived from azatricyclo[4.4.0.02,8]decanone 5 efficiently install the congested spirooxindole functionality of Gelsemine. Depending upon the Heck reaction conditions and the nature of the β-substituent, either products having the natural or unnatural configuration of the spirooxindole group are formed predominantly. Efforts to elaborate the hydropyran ring of Gelsemine from the endo-oriented nitrile substituent of pentacyclic Heck product 18 were unsuccessful. Important steps in the ultimately successful route to (±)-Gelsemine (1) are as follows: (a) intramolecular Heck reaction of tricyclic β-methoxy α,β-unsaturated 2-iodoanilide 68 in the presence of silver phosphate to form pentacyclic product 69 having the unnatural configuration of the spirooxindole fragment, (b) formation of hexacyclic aziridine 80 from the reaction of cyanide with intermediate 79 containing an N-methoxycarbonyl-β-bromoethylamine fragment, (c) introduction of C17 by r...
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use of the intramolecular heck reaction for forming congested quaternary carbon stereocenters stereocontrolled total synthesis of Gelsemine
Journal of the American Chemical Society, 2005Co-Authors: Andrew Madin, David W. Old, Larry E. Overman, Christopher J Odonnell, Matthew J. SharpAbstract:Intramolecular Heck reactions of α,β-unsaturated 2-haloanilides derived from azatricyclo[4.4.0.02,8]decanone 5 efficiently install the congested spirooxindole functionality of Gelsemine. Depending upon the Heck reaction conditions and the nature of the β-substituent, either products having the natural or unnatural configuration of the spirooxindole group are formed predominantly. Efforts to elaborate the hydropyran ring of Gelsemine from the endo-oriented nitrile substituent of pentacyclic Heck product 18 were unsuccessful. Important steps in the ultimately successful route to (±)-Gelsemine (1) are as follows: (a) intramolecular Heck reaction of tricyclic β-methoxy α,β-unsaturated 2-iodoanilide 68 in the presence of silver phosphate to form pentacyclic product 69 having the unnatural configuration of the spirooxindole fragment, (b) formation of hexacyclic aziridine 80 from the reaction of cyanide with intermediate 79 containing an N-methoxycarbonyl-β-bromoethylamine fragment, (c) introduction of C17 by r...
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aza cope rearrangement mannich cyclizations for the formation of complex tricyclic amines stereocontrolled total synthesis of Gelsemine
Journal of the American Chemical Society, 2005Co-Authors: William G. Earley, Jon E. Jacobsen, Andrew Madin, David W. Old, Larry E. Overman, Christopher J Odonnell, Patrick G Meier, Matthew J. SharpAbstract:A detailed examination of the use of aza-Cope rearrangement–Mannich cyclization sequences for assembling the azatricyclo[4.4.0.0 2,8 ]decane core of Gelsemine is described. Iminium ions and Nacyloxyiminium ions derived from endo-oriented 1-methoxy- or 1-hydroxybicyclo[2.2.2]oct-5enylamines do not undergo the first step of this sequence, cationic aza-Cope rearrangement to form cis-hydroisoquinolinium ions. However, the analogous base-promoted oxy-aza-Cope rearrangement does take place to form cis-hydroisoquinolones containing functionality that allows iminium ions or N-acyloxyiminium ions to be generated regioselectively in a subsequent step. Mannich cyclization of cis-hydroisoquinolones prepared in this way efficiently assembles the azatricyclo[4.4.0.0 2,8 ] decane unit of Gelsemine. Using a sequential base-promoted oxy-aza-Cope rearrangement/Mannich cyclization sequence, gram quantities of azatricyclo[4.4.0.0 2,8 ]decanone 18, a central intermediate in our total of (±)-Gelsemine, was prepared from 3-methylanisole in 12 steps and 16% overall yield.
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Total Synthesis of (+/-)-Gelsemine.
Angewandte Chemie (International ed. in English), 1999Co-Authors: Andrew Madin, Christopher J. O'donnell, David W. Old, Larry E. Overman, Matthew J. SharpAbstract:Acomplexmolecularreorganization (1→2), a sequential anionic aza-Cope rearrangement and Mannich cyclization, and an unprecedented intramolecular Heck reaction of the tetrasubstituted double bond of a vinylogous carbamate are key steps in a new total synthesis of (±)-Gelsemine (3). MOM=methoxymethyl, DBU=1,8-diazabicyclo[5.4.0]undec-7-ene.
Samuel J Danishefsky - One of the best experts on this subject based on the ideXlab platform.
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Gelsemine a thought provoking target for total synthesis
Angewandte Chemie, 2003Co-Authors: Samuel J DanishefskyAbstract:Gelsemine and 21-oxoGelsemine have been synthesized through several routes. This Review focuses on the comparison of the different strategies to assemble the bicyclo[3.2.1]octane core, to introduce the bridgehead quaternary C20 to form the pyrrolidine moiety, to construct the oxindole residue, and to close the tetrahydropyran ring en route to Gelsemine.
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Explorations in Organic Chemistry Leading to the Total Synthesis of (±)-Gelsemine
Journal of the American Chemical Society, 2002Co-Authors: Hong Lin, Samuel J DanishefskyAbstract:The total synthesis of (±)-Gelsemine (1) is described. A defining phase of the effort involved recourse to a strategic oxetane ring (see compound 25). It was constructed anticipating an intramolecular displacement of the carbon (C17)−oxygen (O4) bond (see product 48). A key intermediate in the stereospecific elaboration of the oxetane linkage was enone 22, which was susceptible to two β-face attacks leading to 24 and, thence, 25. Three sigmatropic rearrangements were employed in building the bridgehead (C20) and the spiroanilide (C7) quaternary centers en route to Gelsemine.
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explorations in organic chemistry leading to the total synthesis of Gelsemine
Journal of the American Chemical Society, 2002Co-Authors: Hong Lin, Samuel J DanishefskyAbstract:The total synthesis of (±)-Gelsemine (1) is described. A defining phase of the effort involved recourse to a strategic oxetane ring (see compound 25). It was constructed anticipating an intramolecular displacement of the carbon (C17)−oxygen (O4) bond (see product 48). A key intermediate in the stereospecific elaboration of the oxetane linkage was enone 22, which was susceptible to two β-face attacks leading to 24 and, thence, 25. Three sigmatropic rearrangements were employed in building the bridgehead (C20) and the spiroanilide (C7) quaternary centers en route to Gelsemine.
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the synthesis of a key intermediate en route to Gelsemine a program based on intramolecular displacement of the carbonoxygen bond of a strategic oxetane
Tetrahedron Letters, 2002Co-Authors: Hong Lin, Qiang Tan, Samuel J DanishefskyAbstract:The synthesis of key intermediate 30 en route to Gelsemine has been accomplished from known aldehyde 10 via oxetane 19 featuring stereospecific Claisen rearrangement and Lewis acid-catalyzed oxetane ring opening.
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the synthesis of Gelsemine
Tetrahedron Letters, 2002Co-Authors: Hong Lin, Samuel J DanishefskyAbstract:Abstract The synthesis of (±)-Gelsemine has been completed from tetracyclic intermediate 2 via a stereospecific [3,3]-rearrangement followed by a one carbon excision to convert a δ-lactam ( 13 ) to a γ-lactam ( 19 ).
Henk Hiemstra - One of the best experts on this subject based on the ideXlab platform.
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Wacyliminium ion cyclisations in natural product chemistry: Synthesis of Gelsemine
2016Co-Authors: Type Article, Nico W. Speckamp, Nicholas J. Newcombe, Henk Hiemstra, Robert J, Wim-jan KootAbstract:Title N-Acycliminium ion cyclisations in natural product chemistry: synthesis of Gelsemine
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enantioselective synthesis of a key tricyclic intermediateen route to Gelsemine
Tetrahedron Letters, 1999Co-Authors: J. Dijkink, Nico W. Speckamp, Jean-christophe Cintrat, Henk HiemstraAbstract:The efficient synthesis of an enantiopure tricyclic lactam starting from (S)-5-isopropoxypyrrolin-2-one is described. The racemate of this tricyclic lactam is an intermediate in our previously published total synthesis of racemic Gelsemine, so that the present work paves the way for the synthesis of the enantiopure alkaloid. The synthetic route includes a Sonogashira coupling, a highly selective Diels-Alder reaction and a trimethylsilyl triflate-mediatedN-acyliminium ion cyclization as key steps.
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Enantioselective synthesis of a key tricyclic intermediateen route to (+)-Gelsemine
Tetrahedron Letters, 1999Co-Authors: J. Dijkink, W. Nico Speckamp, Jean-christophe Cintrat, Henk HiemstraAbstract:The efficient synthesis of an enantiopure tricyclic lactam starting from (S)-5-isopropoxypyrrolin-2-one is described. The racemate of this tricyclic lactam is an intermediate in our previously published total synthesis of racemic Gelsemine, so that the present work paves the way for the synthesis of the enantiopure alkaloid. The synthetic route includes a Sonogashira coupling, a highly selective Diels-Alder reaction and a trimethylsilyl triflate-mediatedN-acyliminium ion cyclization as key steps.
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The total synthesis of (+)-Gelsemine
J. Chem. Soc. Chem. Commun., 1994Co-Authors: Nicholas J. Newcombe, Henk Hiemstra, R. J. Vijn, W. Nico SpeckampAbstract:Oxindole alkaloids Gelsemine and 21-oxoGelsemine in racemic form are synthesised from sorbic acid.
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the total synthesis of Gelsemine
Journal of The Chemical Society Chemical Communications, 1994Co-Authors: Nicholas J. Newcombe, Henk Hiemstra, R. J. Vijn, Nico W. SpeckampAbstract:Oxindole alkaloids Gelsemine and 21-oxoGelsemine in racemic form are synthesised from sorbic acid.
Kun Yang - One of the best experts on this subject based on the ideXlab platform.
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Characterization of absorbed and produced constituents in goat plasma urine and faeces from the herbal medicine Gelsemium elegans by using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.
Journal of ethnopharmacology, 2020Co-Authors: Meng-ting Zuo, Zi-yuan Wang, Kun Yang, Chong-ying Huang, Yan-chun Liu, Xue-jiao Zhao, Zhao-ying LiuAbstract:Abstract Ethnopharmacological relevance Herbal medicine contains hundreds of natural products, and studying their absorption, metabolism, distribution, and elimination presents great challenges. Gelsemium elegans (G. elegans) is a flowering plants in the Loganiaceae family. The plant is known to be toxic and has been used for many years as a traditional Chinese herbal medicine for the treatment of rheumatoid arthritis, neuropathic pain, spasticity, skin ulcers and cancer. It was also used as veterinary drugs for deworming, promoting animal growth, and pesticides. At present, studies on the metabolism of G. elegans have primarily focused on only a few single available reference ingredients, such as koumine, Gelsemine and gelsedine. Material and methods The goal of this work is to elucidate the overall metabolism of whole G. elegans powder in goats using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS). Results Analyses of plasma, urine and fecal samples identified or tentatively characterized a total of 44 absorbed natural products and 27 related produced metabolites. Gelsedine-type, sarpagine-type and Gelsemine-type alkaloids were the compounds with the highest metabolite formation. In the present study, most natural products identified in G. elegans were metabolized through glucuronidation and oxidation. Hydrogenation, dehydrogenation and demethylation also occurred. Conclusion To our knowledge, this is the first report of the metabolite profiling of the G. elegans crude extract in goats, which is of great significance for a safer and more rational application of this herbal medicine.
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Development and in-house validation of a sensitive LC-MS/MS method for simultaneous quantification of Gelsemine, koumine and humantenmine in porcine plasma.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2018Co-Authors: Kun Yang, Yan-chun Liu, Zhi-liang Sun, Xue-ming Long, Fu-hua Chen, Xiao-feng Liu, Zhao-ying LiuAbstract:Abstract Three monomers of G. elegans indole alkaloids (Gelsemine, koumine and humantenmine) were simultaneously detected in porcine plasma for the first time with the development and validation of a sensitive and reliable LC-ESI-MS/MS method. Using a gradient mobile phase at a constant flow rate of 0.2 mL/min via electrospray ionization (positive ion mode) in a multiple reaction monitoring (MRM) scan, Gelsemine, koumine and humantenmine were eluted, separated and detected at an appropriate retention time. The porcine plasma was prepared using protein precipitation with 1% formic acid-acetonitrile: methanol (2:1, v/v). Using matrix-matched calibration curves and weighted least squares linear regression, a good linearity (r2 > 0.99) was achieved with a concentration range of 0.1–200 μg/L for Gelsemine, koumine and humantenmine; estimated LOD and LOQ values were 0.10 μg/L and 0.2 μg/L, respectively. The mean of the recoveries was in the range of 82.68–100.35% of porcine plasma at four different levels, and the intra-day and inter-day precision (CV) were lower than 15% with a range of 2.46–8.76% and 2.73–10.83%, respectively. The proposed method has proved to be suitable for accurate, quantitative determination of Gelsemine, koumine and humantenmine in porcine plasma.
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identification of Gelsemine metabolites in rat liver s9 by high performance liquid chromatography quadrupole time of flight mass spectrometry
Rapid Communications in Mass Spectrometry, 2018Co-Authors: Kun Yang, Yan-chun Liu, Ya-jun Huang, Zhi-liang Sun, Yi-song Liu, Qi Tang, Sa Xiao, Zhao-ying LiuAbstract:Rationale Gelsemine has been extensively studied because of its anti-tumor, immunomodulatory, insecticidal itching and other significant effect. However, limited information on the pharmacokinetics and metabolism of Gelsemine has been reported. Therefore, the purpose of the present study was to investigate the in vitro metabolism of Gelsemine in rat liver S9 by using a rapid and accurate high-performance liquid chromatography/ quadrupole-time-of-flight mass spectrometry (HPLC/QqTOF-MS). Methods The incubation mixture was processed with 15% trichloroacetic acid. Multiple scans of Gelsemine metabolites and accurate mass measurements were automatically performed simultaneously through data-dependent acquisition in only a 30-min analysis. The structural elucidations of these metabolites were performed by comparing their changes in accurate molecular masses and product ions with those of the parent drug. Results Five metabolites of Gelsemine were identified in rat liver S9. Among of these, four metabolites of Gelsemine were identified for the first time. The present results showed that the metabolic pathways of Gelsemine are oxidation, demethylation, and dehydrogenation in rat liver S9. Conclusions In this study, metabolites of Gelsemine in liver S9 were identified and elucidated firstly using HPLC/QqTOF-MS method. The proposed metabolic pathways of Gelsemine in liver S9 will provide a basis for further studies of the in vivo metabolism of Gelsemine in animals and humans.
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Identification of Gelsemine metabolites in rat liver S9 by high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry.
Rapid communications in mass spectrometry : RCM, 2017Co-Authors: Kun Yang, Yan-chun Liu, Ya-jun Huang, Xiao, Zhi-liang Sun, Yi-song Liu, Qi Tang, Zhao-ying LiuAbstract:Rationale Gelsemine has been extensively studied because of its anti-tumor, immunomodulatory, insecticidal itching and other significant effect. However, limited information on the pharmacokinetics and metabolism of Gelsemine has been reported. Therefore, the purpose of the present study was to investigate the in vitro metabolism of Gelsemine in rat liver S9 by using a rapid and accurate high-performance liquid chromatography/ quadrupole-time-of-flight mass spectrometry (HPLC/QqTOF-MS). Methods The incubation mixture was processed with 15% trichloroacetic acid. Multiple scans of Gelsemine metabolites and accurate mass measurements were automatically performed simultaneously through data-dependent acquisition in only a 30-min analysis. The structural elucidations of these metabolites were performed by comparing their changes in accurate molecular masses and product ions with those of the parent drug. Results Five metabolites of Gelsemine were identified in rat liver S9. Among of these, four metabolites of Gelsemine were identified for the first time. The present results showed that the metabolic pathways of Gelsemine are oxidation, demethylation, and dehydrogenation in rat liver S9. Conclusions In this study, metabolites of Gelsemine in liver S9 were identified and elucidated firstly using HPLC/QqTOF-MS method. The proposed metabolic pathways of Gelsemine in liver S9 will provide a basis for further studies of the in vivo metabolism of Gelsemine in animals and humans.
