Diagnostic fragment‐ion‐based extension strategy for rapid screening and identification of serial components of homologous families contained in traditional Chinese medicine prescription using high‐resolution LC‐ESI‐ IT‐TOF/MS: <i>Shengmai injection</i> as an example

Zheng, Chaonan; Hao, Haiping; Wang, Xuan; Wu, Xiaolan; Wang, Guangji; Sang, Guo-wei; Liang, Yan; Xie, Lin; Xia, Chunhua; Yao, Xilin

doi:10.1002/jms.1502

Cited by 103 publications

(64 citation statements)

References 46 publications

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“…On the basis of a powerful LC/MS-IT-TOF analysis that had been well developed in our laboratory for identification of multiple compounds from a complex matrix a A panel of 10 recombinant human P450 isoforms was screened, and only CYP3A4 and, to a very minor extent, CYP3A5 were found to be active toward the oxygenation metabolism of PPT-type ginsenosides. (Hao et al, 2008a;Zheng et al, 2009), three monooxygenated metabolites for each of the PPT ginsenosides and three monooxygenated and three double-oxygenated metabolites for the aglycone PPT were identified from the microsomal incubation media. As seen from the fragment patterns of both parent compounds and metabolites, the oxygenation metabolism site on the C20 aliphatic branch chain was proposed.…”

Section: Discussionmentioning

confidence: 99%

Microsomal Cytochrome P450-Mediated Metabolism of Protopanaxatriol Ginsenosides: Metabolite Profile, Reaction Phenotyping, and Structure-Metabolism Relationship

Hao

Li²,

Zheng³

et al. 2010

Drug Metab Dispos

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ABSTRACT:Although the biotransformation of ginsenosides in the gastrointestinal tract has been extensively studied, much less is known about hepatic cytochrome P450 (P450)-catalyzed metabolism. The major aims of this study were to clarify the metabolic pathway and P450 isoforms involved and to explore the structure-metabolism relationship of protopanaxatriol (PPT)-type ginsenosides in hepatic microsomes. Efficient depletion of ginsenoside Rh1, Rg2, Rf, and PPT was found, whereas the elimination of Re and Rg1, characterized by a glucose substitution at the C20 hydroxy group, was negligible in microsomal incubation systems. Based on high-performance liquid chromatography hybrid ion trap and time-of-flight mass spectrometry analysis, the oxygenation metabolism on the C20 aliphatic branch chain was identified as the predominant metabolic pathway of PPT ginsenosides in both human and rat hepatic microsomes. By a comparison with authentic standards, the C24-25 double bond was identified as one of the oxygenation sites to produce the metabolites of C20-24 epoxide (ocotillol-type ginsenosides). Both chemical inhibition and human recombinant P450 isoform assays indicated that CYP3A4 was the predominant isozyme responsible for the oxygenation metabolism of PPT ginsenosides. Enzyme kinetic evaluations in rat and human hepatic microsomes and human recombinant CYP3A4 isozyme incubation systems showed generally consistent results in that the intrinsic clearance ranked as Rf < Rg2 < Rh1 < PPT, closely correlating with logP values and the number of glycosyl substitutions. Results obtained from this study suggest that CYP3A4-catalyzed oxygenation metabolism plays an important role in the hepatic disposition of ginsenosides and that glycosyl substitution, especially at the C20 hydroxy group, determines their intrinsic clearances by CYP3A4.

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Section: Discussionmentioning

confidence: 99%

Microsomal Cytochrome P450-Mediated Metabolism of Protopanaxatriol Ginsenosides: Metabolite Profile, Reaction Phenotyping, and Structure-Metabolism Relationship

Hao

Li²,

Zheng³

et al. 2010

Drug Metab Dispos

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“…There are no significant differences between the two forms owing to [12][13][14], however, the chemical information about SMS is still unclear until now. Although different analytical methods for analyzing constituents in ShengMai preparations have been reported, such as highperformance liquid chromatography-evaporative light scattering detector [15], high-performance liquid chromatography-electrospray ionization source/mass spectrometry [12,13,16], high-performance liquid chromatography-diode array detection-mass spectrometry [14], they almost all have some limitations, including long-time separation and low sensitivity. For example, only 17 constitutes were separated and identified in 40 min [14].…”

Section: Introductionmentioning

confidence: 99%

Rapid and global detection and characterization of the constituents in ShengMai San by ultra‐performance liquid chromatography–high‐definition mass spectrometry

Sun

Wei

et al. 2011

J of Separation Science

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An ultra-performance liquid chromatography-high definition mass spectrometry (UPLC-HDMS) method was developed for detection and characterization of the chemical constituents in ShengMai San (SMS), a traditional Chinese medical formula (TCMF). The full-scan LC-MS/MS data sets combined with extra mass were acquired within 14 min using UPLC-HDMS in the MS(E) mode in a single injection. As a result, 92 compounds were identified by comparing the accurate mass and fragments information with that of the authentic standards as well as by MS analysis and the correlative references data. These constituents included ginsenosides, lignans, steroidal saponins and homoisoflavanones. Among them, 25-hydroxyginsenosides were discovered in SMS for the first time. Compare with the previous studies, our research detected more compounds and presented more rapid by applying UPLC-HDMS. It is concluded that a rapid and effective method has been established based on UPLC-HDMS with the utilization of MS(E) , which shows high sensitivity and resolution that is suitable for identifying the constituents of SMS, and this method could be applied to other TCMF.

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“…Among them, the newly developed hybrid ion trap and time-of-flight mass spectrometry (IT-TOF/MS) was selected for its unmatched sensitivity, accuracy, resolution, and high throughput for the identification of complex compounds in addition to its excellent MS n function (Hao et al, 2008;Zheng et al, 2009). Liquid chromatography-hybrid ion trap and time-of-flight mass spectrometry (LC-IT-TOF/MS) has been successfully applied to the global identification of target and nontarget components in Shengmai and Mai-Luo-Ning injection, as well as identification of several drug metabolites (Hao et al, 2008;Zheng et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Development of a Systematic Approach to Identify Metabolites for Herbal Homologs Based on Liquid Chromatography Hybrid Ion Trap Time-of-Flight Mass Spectrometry: Gender-Related Difference in Metabolism of SchisandraLignans in Rats

Liang

Hao²,

Xie³

et al. 2010

Drug Metab Dispos

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ABSTRACT:Metabolic research for herbal medicine (HM) is a formidable task, which is still in its infancy due to complicated components in HM, complex metabolic pathways, and lack of authentic standards. The present work contributes to the development of a powerful technical platform to rapidly identify and classify metabolites of herbal components based on a liquid chromatography hybrid ion trap time-of-flight mass spectrometry. Taking Schisandra lignans extract as an example, the metabolic studies were completed both in vitro and in vivo. In the in vitro study, metabolites for five representative Schisandra lignans were identified and structurally characterized. The major metabolic pathways were summed as demethylation, hydroxylation, and demethylation and hydroxylation. In the in vivo study, 44 metabolites were detected in rat urine. These metabolites were identified and classified rapidly according to the metabolic rules obtained in the in vitro studies, and hydroxylation was confirmed as the primacy metabolic pathway for lignans in rat urine. In addition, "relative cumulative excretion" (RCE) for the metabolites in female and male rats were calculated according to their relative intensities in the urine samples collected at 0 to 12, 12 to 24, and 24 to 36 h. As a result, great gender-related difference on RCE was observed. For most metabolites, RCE in female rats was significantly lower than that in male rats. In conclusion, the presently developed methodology and approach on metabolic research for Schisandra lignans will find its wide use in metabolic studies for herbal medicines.

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Diagnostic fragment‐ion‐based extension strategy for rapid screening and identification of serial components of homologous families contained in traditional Chinese medicine prescription using high‐resolution LC‐ESI‐ IT‐TOF/MS: Shengmai injection as an example

Cited by 103 publications

References 46 publications

Microsomal Cytochrome P450-Mediated Metabolism of Protopanaxatriol Ginsenosides: Metabolite Profile, Reaction Phenotyping, and Structure-Metabolism Relationship

Microsomal Cytochrome P450-Mediated Metabolism of Protopanaxatriol Ginsenosides: Metabolite Profile, Reaction Phenotyping, and Structure-Metabolism Relationship

Rapid and global detection and characterization of the constituents in ShengMai San by ultra‐performance liquid chromatography–high‐definition mass spectrometry

Development of a Systematic Approach to Identify Metabolites for Herbal Homologs Based on Liquid Chromatography Hybrid Ion Trap Time-of-Flight Mass Spectrometry: Gender-Related Difference in Metabolism of SchisandraLignans in Rats

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