• Journal of Ginseng Research
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• v.43 no.4
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• pp.539-549
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• 2019

Background: 20(S)-Protopanaxadiol (PPD), the aglycone part of 20(S)-protopanaxadiol ginsenosides, possesses antidepressant activity among many other pharmacological activities. It is currently undergoing clinical trial in China as an antidepressant. Methods: In this study, an ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass tandem mass spectrometry method was established to identify the metabolites of PPD in human plasma and urine following oral administration in phase IIa clinical trial. Results: A total of 40 metabolites in human plasma and urine were identified using this method. Four metabolites identified were isolated from rat feces, and two of them were analyzed by NMR to elucidate the exact structures. The structures of isolated compounds were confirmed as (20S,24S)-epoxydammarane-12,23,25-triol-3-one and (20S,24S)-epoxydammarane-3,12,23,25-tetrol. Both compounds were found as metabolites in human for the first time. Upon comparing our findings with the findings of the in vitro study of PPD metabolism in human liver microsomes and human hepatocytes, metabolites with m/z 475.3783 and phase II metabolites were not found in our study whereas metabolites with m/z 505.3530, 523.3641, and 525.3788 were exclusively detected in our experiments. Conclusion: The metabolites identified using ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry in our study were mostly hydroxylated metabolites. This indicated that PPD was metabolized in human body mainly through phase I hepatic metabolism. The main metabolites are in 20,24-oxide form with multiple hydroxylation sites. Finally, the metabolic pathways of PPD in vivo (human) were proposed based on structural analysis.

• Journal of Ginseng Research
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• v.44 no.1
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• pp.105-114
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• 2020

Background: Exploring the pharmacokinetic (PK) changes of various active components of single herbs and their combinations is necessary to elucidate the compatibility mechanism. However, the lack of chemical standards and low concentrations of multiple active ingredients in the biological matrix restrict PK studies. Methods: A putative multiple reaction monitoring strategy based on liquid chromatography coupled with mass spectrometry (LC-MS) was developed to extend the PK scopes of quantification without resorting to the use of chemical standards. First, the compounds studied, including components with available reference standard (ARS) and components lacking reference standard (LRS), were preclassified to several groups according to their chemical structures. Herb decoctions were then subjected to ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry analysis with appropriate collision energy (CE) in MS² mode. Finally, multiple reaction monitoring transitions transformed from MS² of ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry were used for ultrahigh-performance liquid chromatography coupled with triple quadrupole mass spectrometry to obtain the mass responses of LRS components. LRS components quantification was further performed by developing an assistive group-dependent semiquantitative method. Results: The developed method was exemplified by the comparative PK process of single herbs Radix Ginseng (RG), Radix Polygala (RP), and their combinations (RG-RP). Significant changes in PK parameters were observed before and after combination. Conclusion: Results indicated that Traditional Chinese Medicine combinations can produce synergistic effects and diminish possible toxic effects, thereby reflecting the advantages of compatibility. The proposed strategy can solve the quantitative problem of LRS and extend the scopes of PK studies.

• Food Science of Animal Resources
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• v.44 no.3
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• pp.651-661
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• 2024

Chicken broth has a taste of umami, and the stewing time has an important effect on the quality of chicken broth, but there are fewer studies on the control of the stewing time. Based on this, the study was conducted to analyze the effects of different stewing times on the sensory, small molecular metabolites, free fatty acids, and volatile flavor compounds contents in chicken broths by liquid chromatography-quadrupole/time-of-flight mass spectrometry, gas chromatography-mass spectrometry, headspace solid-phase microextraction, and gas chromatography-mass spectrometry. Eighty-nine small molecular metabolites, 15 free fatty acids, and 86 volatile flavor compounds were detected. Palmitic and stearic acids were the more abundant fatty acids, and aldehydes were the main volatile flavor compounds. The study found that chicken broth had the best sensory evaluation, the highest content of taste components, and the richest content of volatile flavor components when the stewing time was 2.5 h. This study investigated the effect of stewing time on the quality of chicken broth to provide scientific and theoretical guidance for developing and utilizing local chicken.

• Journal of Ginseng Research
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• v.37 no.3
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• pp.371-378
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• 2013

Serum and liver metabolites in rats fed red ginseng (RG) were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. The mass data were analyzed by partial least squares-discriminant analysis (PLS-DA) to discriminate between control and RG groups and identify metabolites contributing to this discrimination. The RG group was clearly separated from the control group on PLS-DA scores plot for serum samples, but not liver samples. The major metabolites contributing to the discrimination included lipid metabolites (lysophosphatidylcholine, acyl-carnitine, and sphingosine), isoleucine, nicotinamide, and corticosterone in the serum; the blood levels of all but isoleucine were reduced by RG administration. Not all metabolites were positively correlated with the health benefits of RG. However, the blood levels of lysophosphatidylcholine, which stimulate various diseases, and long-chain acylcarnitines and corticosterone, which activate the stress response, were reduced by RG, suggesting long-term RG might relieve stress and prevent physiological and biological problems.

• Journal of Life Science
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• v.29 no.2
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• pp.198-201
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• 2019

Recently, it has been reported that Bacillus mojavensis possesses antifungal properties and plant growth-promoting activities, which are similar to the characteristics of siderophore. In this study, the siderophore produced by B. mojavensis was assessed using a solid phase extraction (SPE) cartridge and liquid chromatography quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS/MS). After B. mojavensis was incubated in phenol medium for 16 hr and lyophilized, the sample was dissolved in water and loaded to an SPE cartridge to remove interferences. The cartridge was washed with 5% methanol in water and eluted with 2% formic acid in methanol sequentially. The eluted solution was evaporated under a stream of nitrogen gas and reconstituted in methanol. The reconstituted sample was filtered, and $1{\mu}l$ of the sample was assessed using Q-TOF MS/MS. The mass spectrometer was operated using the positive electrospray ionization mode. Based on the mass spectrum and tandem mass spectrum, the siderophore produced by B. mojavensis was bacillibactin, one of the catechol types of siderophore with a molecular weight of 882.2556. This siderophore analysis could provide a justification for the study of B. mojavensis as a functional food and for pharmaceutical applications.

• Mass Spectrometry Letters
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• v.14 no.1
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• pp.1-8
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• 2023

Eutylone, dibutylone, and dimethylone are potential psychotropic designer drugs. The purpose of this study was to investigate the in vitro metabolic pathways of synthetic cathinones with methylenedioxy groups. The three methylenedioxy derivatives were incubated with human liver microsomes. The metabolites were characterized based on liquid chromatography and quadrupole-time-of-flight mass spectrometry. Eutylone, dibutylone, and dimethylone were metabolized to yield three, six, and four metabolites, respectively. Reduction and demethylenation were the major metabolic pathways for all three drugs tested. However, dibutylone and dimethylone showed an additional metabolite generated via N-oxidation. These results provide evidence for the in vivo metabolism of methylenedioxy synthetic cathinones, and could be applied to the analysis of synthetic cathinones and their relevant metabolites in biological samples.

• Journal of Rheumatic Diseases
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• v.24 no.4
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• pp.192-202
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• 2017

Objective. Rebampide is a gastroprotective agent used to treat gastritis. It possesses anti-inflammatory and anti-arthritis effects, but the mechanisms of these effects are not well understood. The objective of this study was to explore mechanisms underlying the therapeutic effects of rebamipide in inflammatory arthritis. Methods. Collagen-induced arthritis (CIA) was induced in DBA/1J mice. DBA/1J mice were immunized with chicken type II collagen, then treated intraperitoneally with rebamipide (10 mg/kg or 30 mg/kg) or vehicle (10% carboxymethylcellulose solution) alone. Seven weeks later, plasma samples were collected. Plasma metabolic profiles were analyzed using ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics study and metabolite biomarkers were identified through multivariate data analysis. Results. Low dose rebamipide treatment reduced the clinical arthritis score compared with vehicle treatment, whereas high dose rebamipide in CIA aggravated arthritis severity. Based on multivariate analysis, 17 metabolites were identified. The plasma levels of metabolites associated with fatty acids and phospholipid metabolism were significantly lower with rebamipide treatment than with vehicle. The levels of $15-deoxy-^{{\Delta}12,14}$ prostaglandin J2 and thromboxane B3 decreased only in high dose-treated groups. Certain peptide molecules, including enterostatin (VPDPR) enterostatin and bradykinin dramatically increased in rebamipide-treated groups at both doses. Additionally, corticosterone increased in the low dose-treated group and decreased in the high dose-treated group. Conclusion. Metabolomics analysis revealed the anti-inflammatory effects of rebamipide and suggested the potential of the drug repositioning in metabolism- and lipid-associated diseases.

• Journal of Ginseng Research
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• v.38 no.3
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• pp.187-193
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• 2014

Background: White ginseng (Panax ginseng Meyer) is commonly distributed as a health food in food markets. However, there is no practical method for distinguishing Korean white ginseng (KWG) from Chinese white ginseng (CWG), except for relying on the traceability system in the market. Methods: Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry combined with orthogonal partial least squares discrimination analysis (OPLS-DA) was employed to discriminate between KWG and CWG. Results: The origins of white ginsengs in two test sets ($1.0{\mu}L$ and $0.2{\mu}L$ injections) could be successfully discriminated by the OPLS-DA analysis. From OPLS-DA S-plots, KWG exhibited tentative markers derived from ginsenoside Rf and notoginsenoside R3 isomer, whereas CWG exhibited tentative markers derived from ginsenoside Ro and chikusetsusaponin Iva. Conclusion: Results suggest that ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry coupled with OPLS-DA is an efficient tool for identifying the difference between the geographical origins of white ginsengs.

• Journal of Applied Biological Chemistry
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• v.62 no.4
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• pp.433-439
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• 2019

Artemisia species are widely used as food ingredients and raw material in traditional medicine. However, to date, the secondary metabolites of Artemisia gmelinii Weber ex Stechm. have not been sufficiently investigated. The secondary metabolites of A. gmelinii, which was collected from representative regions in Chungbuk, Gangwon, and Gyeongbuk, were analyzed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTof MS) combined with an unsupervised principal component analysis (PCA) multivariate analysis. In the loading scatter plot of PCA, significant changes in metabolites were observed between the regions, ten metabolites (3: 5-O-caffeoylquinic acid, 4: 4-O-caffeoylquinic acid, 8: trans-melilotoside, 12: quercetin 3-O-hexoside, 15: 3,4-O-dicaffeoylquinic acid, 17: 3,5-O-dicaffeoylquinic acid, 18: 4,5-O-dicaffeoylquinic acid, 19: syringaldehyde, 20: caffeoylquinic acid derivative, and 23: icariside II) were evaluated as key markers among twenty-five identified metabolites. Interestingly, the contents of the identified marker significantly differed between the three groups. This is the first study to report the presence of marker metabolites and their correlating geographical cultivation in A. gmelinii.

• Mass Spectrometry Letters
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• v.13 no.4
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• pp.95-105
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• 2022

Amatoxin-induced mushroom poisoning starts with nonspecific symptoms of toxicity but hepatic damage may follow, resulting in the rapid development of liver insufficiency and, ultimately, coma and death. Accurate detection of amatoxins, such as α-, β-, and γ-amanitin, within the first few hours after presentation is necessary to improve the therapeutic outcomes of patients. Therefore, analytical methods for the identification and quantification of α-, β-, and γ-amanitin in biological samples are necessary for clinical and forensic toxicology. This study presents a literature review of the analytical techniques available for amatoxin detection in biological matrices, and established an inventory of liquid chromatography (LC) techniques with mass spectrometry (MS), ultraviolet (UV) detection, and electrochemical detection (ECD). LC-MS methods using quadrupole tandem mass spectrometry, time-of-flight mass spectrometry, and orbitrap MS are powerful analytical techniques for the identification and determination of amatoxins in plasma, urine, serum, and tissue samples, with high sensitivity, specificity, and reproducibility compared to LC with UV and ECD, enzyme-linked immunoassay, and capillary electrophoresis methods.