-
[show abstract]
[hide abstract]
ABSTRACT: A metabolomics strategy based on rapid resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS) and multivariate statistics has been implemented to identify potential biomarkers in uterine cervix cancer. Due to the importance of the data pre-processing method, three popular software packages have been compared. Then they have been used to acquire respective data matrices from the same LC-MS/MS data. Multivariate statistics was subsequently used to identify significantly changed biomarkers for uterine cervix cancer from the resulting data matrices. The reliabilities of the identified discriminated metabolites have been further validated on the basis of manually extracted data and ROC curves. Nine potential biomarkers have been identified as having a close relationship with uterine cervix cancer. Considering these in combination as a biomarker group, the AUC amounted to 0.997, with a sensitivity of 92.9% and a specificity of 95.6%. The prediction accuracy was 96.6%. Among these potential biomarkers, the amounts of four purine derivatives were greatly decreased, which might be related to a P2 receptor that might lead to a decrease in cell number through apoptosis. Moreover, only two of them were identified simultaneously by all of the pre-processing tools. The results have demonstrated that the data pre-processing method could seriously bias the metabolomics results. Therefore, application of two or more data pre-processing methods would reveal a more comprehensive set of potential biomarkers in non-targeted metabolomics, before a further validation with LC-MS/MS based targeted metabolomics in MRM mode could be conducted.
The Analyst 03/2013; · 4.23 Impact Factor
-
Jing Xu,
Yanhua Chen, Ruiping Zhang,
Yongmei Song,
Jianzhong Cao,
Nan Bi,
Jingbo Wang,
Jiuming He,
Jinfa Bai,
Lijia Dong,
Lvhua Wang,
Qimin Zhan,
Zeper Abliz
[show abstract]
[hide abstract]
ABSTRACT: Diagnostic and therapeutic biomarkers useful for esophageal squamous cell carcinoma (ESCC) have the ability to increase the long term survival of cancer patients. A metabolomics study, using plasma from four groups including ESCC patients before, during and after chemoradiotherapy (CRT) and healthy controls, was originally carried out by LC-MS to determine global alterations in the metabolic profiles and find biomarkers potentially applicable to diagnosis and monitoring treatment effects. It is worth pointing out that a clear clustering and separation of metabolic data from the four groups was observed, which indicated that disease status and treatment intervention resulted in specific metabolic perturbations in the patients. A series of metabolites were found to be significantly altered in ESCC patients vs. healthy controls and in pre- vs. post-treatment patients based on multivariate statistical data analysis (MVDA). In order to further validate the reliability of these potential biomarkers, an independent validation was performed by using the multiple reaction monitoring (MRM) based targeted approach. Finally, 18 most significantly altered plasma metabolites in ESCC patients, relative to healthy controls, were tentatively identified as lysophosphatidylcholines (lysoPCs), fatty acids, L-carnitine, acylcarnitines, organic acids and a sterol metabolite. The classification performance of these metabolites were analysed by receiver operating characteristic (ROC) analysis and a biomarker panel was generated. Together, biological significance of these metabolites was discussed. Comparison between pre- and post-treatment patients generated 11 metabolites as potential therapeutic biomarkers which were tentatively identified as amino acids, acylcarnitines and lysoPCs. Levels of three of these (ToctanoylcarnitineT, TlysoPC(16:1), and decanoylcarnitine)T were closely correlated with treatment effect. Moreover, variation of these three potential biomarkers was investigated over the treatment course. The results suggest that these biomarkers may be useful in diagnosis, as well as in monitoring therapeutic responses and predicting outcomes of the ESCC.
Molecular & Cellular Proteomics 02/2013; · 7.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Metabonomics is an important platform for investigating the metabolites of integrated living systems and their dynamic responses to changes caused by both endogenous and exogenous factors. A metabonomics strategy based on LC-MS/MS in both positive and negative ion modes was applied to investigate the short-term and long-term stability of metabolites in plasma. Principal components analysis (PCA) and ten kinds of identified metabolites were used to summarize the time-dependent change rules in metabolites systematically at different temperatures. The long-term stability of metabolites in plasma specimens stored at -80 °C for five years was also studied. Analysis of these subjects identified 36 metabolites with statistically significant changes in expression (p<0.05) and found a kind of metabolites with hundred-fold change. The stability of metabolites in blood at 4 °C for 24 h was also investigated. These studies show that a thorough understanding of the effects of metabolite stability are necessary for improving the reliability of potential biomarkers.
Analytical Chemistry 02/2013; · 5.86 Impact Factor
-
Zhigang Luo,
Jiuming He,
Yi Chen,
Jingjing He,
Tao Gong,
Fei Tang,
Xiaohao Wang, Ruiping Zhang,
Lan Huang,
Lianfeng Zhang,
Haining Lv,
Shuang-Gang Ma,
Zhaodi Fu,
Xiaoguang Chen,
Shi-Shan Yu,
Zeper Abliz
[show abstract]
[hide abstract]
ABSTRACT: Whole-body molecular imaging is able to directly map spatial distribution of molecules and monitor its biotransformation in intact biological tissue sections. Imaging mass spectrometry (IMS), a label-free molecular imaging method, can be used to image multiple molecules in a single measurement with high specificity. Herein, a novel easy-to-implement, whole-body IMS method was developed with air flow-assisted ionization in a DESI mode (AFA-DESI). The developed IMS method can effectively image molecules in a large whole-body section in open air without sample pretreatment, such as chemical labeling, section division or matrix deposition. Moreover, the signal levels were improved and the spatial assignment errors were eliminated, thus high-quality whole-body images were obtained. With this novel IMS method, in situ mapping analysis of molecules was performed in adult rat sections with picomolar sensitivity under ambient conditions, and the dynamic information of molecule distribution and its biotransformation was provided to uncover molecular events at the whole-animal level. A global view of the differential distribution of an anticancer agent and its metabolites was simultaneously acquired in whole-body rat and model mouse bearing neuroglioma along the administration time. The obtained drug distribution provided rich information for identifying the targeted organs, and predicting possible tumor spectrum, pharmacological activity and potential toxicity of drug candidates.
Analytical Chemistry 02/2013; · 5.86 Impact Factor
-
Yaping Tian,
Jiuming He, Ruiping Zhang,
Haining Lv,
Shuanggang Ma,
Yanhua Chen,
Shishan Yu,
Xiaoguang Chen,
Yan Wu,
Wenyi He,
Zeper Abliz
[show abstract]
[hide abstract]
ABSTRACT: An integrated approach combining data acquisition using MS(E) and multi-period product ion scan (mpMS/MS), with high-resolution characteristic extracted ion chromatograms (hcXIC) as a data mining method, was developed for in vivo drug metabolites screening and identification. This approach is illustrated by analyzing metabolites of a potential anticancer agent, 3,6,7-trimethoxyphenanthroindolizidine (CAT) in rat urine based on rapid resolution liquid chromatography combined with tandem mass spectrometry (RRLC-MS/MS). Untargeted full-scan MS(E) enabled the high-throughput acquisition of potential metabolites, and targeted mpMS/MS contributed to the sensitivity and specificity of the acquisition of molecules of interest. The data processing method hcXIC, based on the structure of CAT, was shown to be highly effective for the metabolite discovery. Through the double-filtering effect of the characteristic ion and accurate mass, conventional extracted ion chromatograms that contained a substantial number of false-positive peaks were simplified into chromatograms essentially free of endogenous interferences. As a result, 21 metabolites were detected in rat urine after oral administration of CAT. Based on the characteristic fragmentation patterns of the phenanthroindolizidine alkaloid, the structures of 9 metabolites were identified. Furthermore, the interpretation of the MS/MS spectra of these metabolites enabled the determination of demethylation position as well as the differentiation between N-oxidized and hydroxylated metabolites.
Analytica chimica acta 06/2012; 731:60-7. · 4.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A rapid, sensitive, specific and accurate analytical method of ultra-fast liquid chromatography combined with tandem mass spectrometry (UFLC-MS/MS) was established for simultaneous quantitative analysis of 16 distinct endogenous estrogens and their metabolites (EMs) in postmenopausal female urine. The quantitative method utilized a hydrolysis/extraction/derivatization step and a UFLC system to achieve separation in 16 min. The lower limit of quantitation for each estrogen metabolite was 2 pg mL(-1) with the percent recovery of a known added amount of estrogen at 93.2-109.3%. The intra-batch accuracy and precision for all analytes were 87.5-107.7% and 0.6-11.7%, respectively, while inter-batch accuracy and precision were 87.0-105.8% and 1.2-10.2%, respectively. Using this developed and validated method, the comprehensive metabolic profiling of 16 EMs in urine samples of 86 postmenopausal female breast cancer patients and 36 healthy controls was investigated by systematic statistical analysis. As a result, the circulating levels of 6 EMs were found to be different by a comparison of patients and healthy controls. The parent estrogens, estrone (E1) and 17β-estradiol (E2), as well as 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2) were produced in higher abundance, whereas 16α-hydroxyestrone (16α-OHE1) and 2-methoxyestradiol (2-MeOE2) were decreased in the breast cancer group. 2-OHE2 and 4-OHE2 in particular showed significant elevation in patients, which are consistent with the carcinogenic mechanism hypothesis that catechol estrogens can react with DNA via quinones, resulting in mutations to induce breast cancer. Thus, 2,4-hydroxylation may be the dominant metabolic pathway for parent estrogens rather than 16α-hydroxylation. The lower level of 2-MeOE2 in the breast cancer group was believed to correlate with its protective effect against tumor formation. This study could provide valuable information on the association of the EM metabolic pathway with carcinogenesis as well as identify potential biomarkers for estrogen-induced breast cancer risk.
Analytica chimica acta 01/2012; 711:60-8. · 4.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Ambient ionization methods are an important research area in mass spectrometry (MS) analysis. Under ambient conditions, the gas flow and atmospheric pressure significantly affect the transfer and focusing of ions. The design and implementation of air flow assisted ionization (AFAI) as a novel and effective, remote sampling method for ambient mass spectrometry are described herein. AFAI benefits from a high extracting air flow rate. A systematic investigation of the extracting air flow in the AFAI system has been carried out, and it has been demonstrated not only that it plays a role in the effective capture and remote transport of charged droplets, but also that it promotes desolvation and ion formation, and even prevents ion fragmentation during the ionization process. Moreover, the sensitivity of remote sampling ambient MS analysis was improved significantly by the AFAI method. Highly polar and nonpolar molecules, including dyes, pharmaceutical samples, explosives, drugs of abuse, protein and volatile compounds, have been successfully analyzed using AFAI-MS. The successful application of the technique to residue detection on fingers, large object analysis and remote monitoring in real time indicates its potential for the analysis of a variety of samples, especially large objects. The ability to couple this technique with most commercially available MS instruments with an API interface further enhances its broad applicability.
Rapid Communications in Mass Spectrometry 04/2011; 25(7):843-50. · 2.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A metabonomic approach based on complementary hydrophilic interaction chromatography and reversed-phase liquid chromatography combined with tandem mass spectrometry and time-course analysis of metabolites was implemented to find more reliable potential biomarkers in urine of Walker 256 tumor-bearing rats. A major challenge in metabonomics is distinguishing reliable biomarkers that are closely associated with the genesis and progression of diseases from those that are unrelated but altered significantly. In this study, these biomarkers were selected according to the change trends of discriminating metabolites during the genesis and progression of cancer. Seven consecutive batches of urine samples from preinoculation to 16 days after were collected and analyzed. Multivariate analysis revealed 87 discriminating metabolites. Time-course analysis of discriminating metabolites was used to select more reliable biomarkers with regular and reasonable change trends. Finally, 47 were found and 15 were identified including 12 carnitine derivatives, 2 amino acid derivatives, 1 nucleoside. On the basis of time-course behaviors of these potential biomarkers, we hypothesize such disruption might result from elevated cell proliferation, reduced β-oxidation of fatty acids, and poor renal tubular reabsorption. These studies demonstrate that this method can help to find more reliable potential biomarkers and provide valuable biochemical insights into metabolic alterations in tumor-bearing biosystems.
Journal of Proteome Research 02/2011; 10(4):1953-61. · 5.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: It had been reported that cordycepin could activate AMP-activated protein kinase. One possible mechanism is that cordycepin mediated AMP-activated protein kinase activation by conversion into cordycepin monophosphate, which acts as an AMP analog to activate AMP-activated protein kinase. To confirm the aforementioned hypothesis, we investigate the binding of cordycepin monophosphate to AMP-activated protein kinase using molecular docking. The modeling results indicate that cordycepin monophosphate binds to AMP-activated protein kinase with high affinity. The hydrogen bonds provide attractive forces between molecules. Our results further identify the key residues contributing to the interaction. Also, the modeling results predict that cordycepin monophosphate and AMP would have similar binding modes with AMP-activated protein kinase. Further investigation of AMP-activated protein kinase activation in vitro provides the evidence that cordycepin monophosphate functioned as an AMP mimic to activate AMP-activated protein kinase.
Chemical Biology & Drug Design 10/2010; 76(4):340-4. · 2.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: An integrated ionization approach of electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and atmospheric pressure photoionization (APPI) combining with rapid resolution liquid chromatography mass spectrometry (RRLC-MS) has been developed for performing global metabonomic analysis on complex biological samples. This approach was designed to overcome the low ionization efficiencies of endogenous metabolites due to diverse physicochemical properties as well as ion suppression, and obtain comprehensive metabolite profiles in LC-MS analysis. Ionization capability and applicability were manifested by improved ionization efficiency and enlarged metabolite coverage in analysis on typical urinary metabolite standards and urine samples from healthy volunteers. The method was validated by the limit of detection and precision. When applied to the global metabonomic studies of lung cancer, more comprehensive biomarker candidates were obtained to reflect metabolic traits between healthy volunteers and lung cancer patients, including 74 potential biomarkers in positive ion mode and 59 in negative ion mode. Taking identical potential biomarkers of any two or three ionization methods into account, analysis using ESI-MS in positive (+) and negative (-) ion mode contributed to 70 and 64% of the total potential biomarkers, respectively. The biomarker discovery capability of (+/-) APCI-MS accounted for 45 and 42% of the overall; meanwhile (+/-) APPI-MS amounted for 39 and 54%. These results indicated that potential biomarkers with vital biological information could be missed if only a single ionization method was used. Furthermore, 11 potential biomarkers were identified including amino acids, nucleosides, and a metabolite of indole. They revealed elevated amino acid and nucleoside metabolism as well as protein degradation in lung cancer patients. This proposed approach provided a more comprehensive picture of the metabolic changes and further verified identical biomarkers that were obtained simultaneously using different ionization methods.
Journal of Proteome Research 08/2010; 9(8):4071-81. · 5.11 Impact Factor
-
Biological Mass Spectrometry 07/2010; 45(7):824-8. · 3.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A metabonomics strategy based on rapid resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS), multivariate statistics and metabolic correlation networks has been implemented to find biologically significant metabolite biomarkers in breast cancer. RRLC-MS/MS analysis by electrospray ionization (ESI) in both positive and negative ion modes was employed to investigate human urine samples. The resulting data matrices were analyzed using multivariate analysis. Application of orthogonal projections to latent structures discriminate analysis (OPLS-DA) allowed us to extract several discriminated metabolites reflecting metabolic characteristics between healthy volunteers and breast cancer patients. Correlation network analysis between these metabolites has been further applied to select more reliable biomarkers. Finally, high resolution MS and MS/MS analyses were performed for the identification of the metabolites of interest. We identified 12 metabolites as potential biomarkers including amino acids, organic acids, and nucleosides. They revealed elevated tryptophan and nucleoside metabolism as well as protein degradation in breast cancer patients. These studies demonstrate the advantages of integrating metabolic correlation networks with metabonomics for finding significant potential biomarkers: this strategy not only helps identify potential biomarkers, it also further confirms these biomarkers and can even provide biochemical insights into changes in breast cancer.
The Analyst 10/2009; 134(10):2003-11. · 4.23 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Abundant evidence has suggested that neuroinflammation participates in the pathogenesis of Parkinson's disease (PD). The emerging evidence has supported that microglia may play key roles in the progressive neurodegeneration in PD and might be a promising therapeutic target. Ganoderma lucidum (GL), a traditional Chinese medicinal herb, has been shown potential neuroprotective effects in our clinical trials that make us to speculate that it might possess potent anti-inflammatory and immunomodulating properties. To test this hypothesis, we investigated the potential neuroprotective effect of GL and possible underlying mechanism of action through protecting microglial activation using co-cultures of dopaminergic neurons and microglia. The microglia is activated by LPS and MPP(+)-treated MES 23.5 cell membranes. Meanwhile, GL extracts significantly prevent the production of microglia-derived proinflammatory and cytotoxic factors [nitric oxide, tumor necrosis factor-α (TNF-α), interlukin 1β (IL-1β)] in a dose-dependent manner and down-regulate the TNF-α and IL-1β expressions on mRNA level as well. In conclusion, our results support that GL may be a promising agent for the treatment of PD through anti-inflammation.
Evidence-based Complementary and Alternative Medicine 08/2009; 2011:156810. · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To develop a high performance liquid chromatography method for simultaneous determination of tour active constituents, dactylorhin B, loroglossin, dactylorhin A, militarine present in a Tibetan herb Gymnadenia conopsea.
The analysiswas achieved on a Pravil C18 column (4.6 mm x 150 mm, 5 microm) eluted with the mobile phases of methanol (A)-water (B) in gradient elution. The initial condition was 15% A, chsnhrf to 20% A in 10 min, to 45% A in 10 min, to 70% A in 15 min. The detection wavelength was set at 222 nm. The flow rate was 0.7 mL x min(-1). Orthogonal test was adopted to optimize extraction process of four active compounds from Gymnadenia conopsea.
The assay displayed good linearity over the concentration ranges of 0.20-4.05 microg (r = 0.9999), 0.10-5.11 micro g (r = 0.9999), 0.10-5.11 microg (r = 0.9999) and 0.09-1.79 microg (r = 0.9999), respectively. The average recoveries (n=9) were 99.19%, 99.16%, 99.52% and 99.00% for dactylorhin B, loroglossin, dactylorhin A and militarine respectively.
The method is simple, sensitive, reliable and reproducible which can be used for the quality study of Gymnadenia conopsea.
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 07/2009; 34(14):1819-22.
-
Rapid Communications in Mass Spectrometry 05/2009; 23(10):1519-24. · 2.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The fragmentation behavior of hydroquinone glycosides involving one or two sugar groups from Fraxinus sieboldiana and their analogue arbutin was investigated systematically by electrospray ionization tandem mass spectrometry in negative ion mode. The characteristic fragmentation reaction of these compounds was through the homolytic and heterolytic cleavage of the O-glycosidic bond to produce radical aglycone ion ([Y0-H]-*) and aglycone ion (Y0-), respectively. Unambiguous differentiation between the mono-O-glycoside isomers which differ in glycosylation position was achieved by comparing the relative abundance of [Y0-H]-* and Y0- ions with the optimized collision energy. In the fragmentation of 1, 4-di-O-glycosides, only the Y0- ion was produced when the first glucosyl residue was expelled. However, both the [Y0-H]-* and Y0- ions were present when the second glucosyl residue was eliminated. In addition, an interesting [Y0-2H]- ion was present in the product ion spectra of hydroquinone glycosides with methoxy group(s) substituted at C-3 or/and C-5 positions of the benzene ring. The results of this study can facilitate the rapid determination of hydroquinone glycosides in crude plant extracts and also reveal that the systematic investigation and optimization of collision energy play an important role in the differentiation of isomers which have subtle differences in structures.
Biological Mass Spectrometry 05/2009; 44(8):1182-7. · 3.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: NMR and LC-MS combined with an incompleted separation strategy were proposed to the simultaneous structure identification of natural products in crude extracts, and a novel method termed as NMR/LC-MS parallel dynamic spectroscopy (NMR/LC-MS PDS) was developed to discover the intrinsic correlation between retention time (Rt), mass/charge (m/z) and chemical shift (delta) data of the same constituent from mixture spectra by the co-analysis of parallelly visualized multispectroscopic datasets from LC-MS and (1)H NMR. The extracted ion chromatogram (XIC) and (1)H NMR signals deriving from the same individual constituent were correlated through fraction ranges and intensity changing profiles in NMR/LC-MS PDS spectrum due to the signal amplitude co-variation resulted from the concentration variation of constituents in a series of incompletely separated fractions. NMR/LC-MS PDS was applied to identify 12 constituents in an active herbal extract including flavonol glycosides, which was separated into a series of fractions by flash column chromatography. The complementary spectral information of the same individual constituent in the crude extract was discovered simultaneously from mixture spectra. Especially, two groups of co-eluted isomers were identified successfully. The results demonstrated that NMR/LC-MS PDS combined with the incompleted separation strategy achieved the similar function of on-line LC-NMR-MS analysis in off-line mode and had the potential for simplifying and accelerating the analytical routes for structure identification of constituents in herbs or their active extracts.
Analytica chimica acta 02/2009; 632(2):221-8. · 4.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Coldspray ionization (CSI) mass spectrometry, a variant of electrospray ionization (ESI) operating at low temperature (20 to -80 degrees C), has been used to characterize protein conformation and noncovalent complexes. A comparison of CSI and ESI was presented for the investigation of the equilibrium acid-induced unfolding of cytochrome c, ubiquitin, myoglobin, and cyclophilin A (CypA) over a wide range of pH values in aqueous solutions. CSI and nanoelectrospray ionization (nanoESI) were also compared in their performance to characterize the conformational changes of cytochrome c and myoglobin. Significant differences were observed, with narrower charged-state distribution and a shift to lower charge state in the CSI mass spectra compared with those in ESI and nanoESI mass spectra. The results suggest that CSI is more prone to preserving folded protein conformations in solution than the ESI and nanoESI methods. Moreover, the CSI-MS data are comparable with those obtained by other established biophysical methods, which are generally acknowledged to be the suitable techniques for monitoring protein conformation in solution. Noncovalent complexes of holomyoglobin and the protein-ligand complex between CypA and cyclosporin A (CsA) were also investigated at a neutral pH using the CSI-MS method. The results of this study suggest the ability of CSI-MS in retaining of protein conformation and noncovalent interactions in solution and probing subtle protein conformational changes. Additionally, the CSI-MS method is capable of analyzing quantitatively equilibrium unfolding transitions of proteins. CSI-MS may become one of the promising techniques for investigating protein conformation and noncovalent protein-ligand interactions in solution.
Journal of the American Society for Mass Spectrometry 02/2009; 20(5):845-51. · 4.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A rapid method combining liquid chromatography with electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) was developed for the determination of the hydroxyl radical (.OH). .OH generated via Fenton reaction was spin-trapped by 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and then analyzed by LC/ESI-MS/MS in multiple reaction monitoring (MRM) mode, using N-methyl-2-pyrrolidone (NMP) as the internal standard. The peak area ratio of DMPO-OH to NMP positively correlated with the concentration of .OH. The relative standard deviation (RSD) of the method was 1.13% (n = 8). The present method was successfully applied to evaluate the .OH scavenging capacity of several phenolic acids.
Rapid Communications in Mass Spectrometry 02/2007; 21(2):107-11. · 2.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A method of fast profiling the constituents in an active herbal extract and their metabolites in biological fluids based on the combination of fragmentation behavior and metabolic pathways is described. The complementary information from fragmentation behavior and metabolic pathways helped not only to identify the structure of parent constituents and metabolites, but also to correlate metabolites back to their parent forms. An active fraction obtained from Gossypium herbaceam L., named AB-8-2, and bile samples from rats administered it orally and intravenously were analyzed using high-performance liquid chromatography/multi-stage tandem mass spectrometry (HPLC-MSn) in a single chromatographic run. Fifty-eight flavonols comprising mixed sulfate, methyl, glucuronide and glycoside derivatives of quercetin or kaempferol were detected, including several groups of isomers. By contrasting the analytical results from AB-8-2 and from bile samples derived from different administration routes, a profile of the biotransformation of the flavonols in AB-8-2 was obtained. The results should be of benefit in targeting potential active ingredients in complex mixtures, such as herbs or their active extracts.
Rapid Communications in Mass Spectrometry 02/2007; 21(12):1877-88. · 2.79 Impact Factor
