• Analytical Science and Technology
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• v.28 no.2
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• pp.132-138
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• 2015

Rosiglitazone metabolites in rat plasma were analyzed after intraperitoneal and oral administration to rats. Seven metabolites (M1-M7) were detected in rat plasma (IP and PO), and the structures were confirmed using liquid chromatography-triple time of flight (TOF) mass spectrometry; as a result, the most abundant metabolite was M5, a de-methylated rosiglitazone. Other minor in vivo metabolites were driven from monooxygenation and demethylation (M2), thiazolidinedione ring-opening (M1, M3), mono-oxygenation (M4, M7), and mono-oxygenation followed by sulfation (M6). Among them, M1 was found to be a 3-{p-[2-(N-methyl-N-2-pyridylamino)ethoxy]phenyl}-2-(methylsulfinyl)propionamide, which is a novel metabolite of rosiglitazone. There was no significant difference in the metabolic profiles resulting from the two administrations. The findings of this study provide the first comparison of circulating metabolite profiles of rosiglitazone in rat after IP and PO administration and a novel metabolite of rosiglitazone in rat plasma.

• Bulletin of the Korean Chemical Society
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• v.26 no.5
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• pp.729-734
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• 2005

A sensitive and selective method for quantitation of sofalcone and its active metabolite in human plasma has been established using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI/MS/MS). Plasma samples were transferred into 96-well plate using an automated sample handling system and spiked with 10 $\mu$L of 2 $\mu$g/mL $d_3$-sofalcone and $d_3$-sofalcone metabolite solutions (internal standard), respectively. After adding 0.5 mL of acetonitrile to the 96-well plate, the plasma samples were then vortexed for 30 sec. After centrifugation, the supernatant was transferred into another 96-well plate and completely evaporated at 40 ${^{\circ}C}$ under a stream of nitrogen. Dry residues were reconstituted with mobile phase and were injected into a $C_{18}$ reversed-phase column. The limit of quantitation of sofalcone and its metabolite was 2 ng/mL, using a sample volume of 0.2 mL for analysis. The reproducibility of the method was evaluated by analyzing 10 replicates over the concentration range of 2 ng/mL to 1000 ng/mL. The validation experiments of the method have shown that the assay has good precision and accuracy. Sofalcone and its metabolite produced a protonated precursor ion ([M+H]$^+$) of m/z 451 and 453, and a corresponding product ion of m/z 315 and 317, respectively. Internal standard ($d_3$-sofalcone and $d_3$-sofalcone metabolite) produced a protonated precursor ion ([M+H]$^+$) of m/z 454 and 456 and a corresponding product ion of m/z 315 and 317, respectively. The method has been successfully applied to a pharmacokinetic study of sofalcone and its active metabolite in human plasma.

• Journal of Microbiology and Biotechnology
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• v.17 no.10
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• pp.1717-1720
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• 2007

In the course of screening for nitric oxide inhibitors in activated microglial BV-2 cells, cyclo(dehydrohistidyl-L-tryptophyl) was isolated from solid-state fermentation cultures of an unidentified fungal strain, Fb956. Its structure was determined by spectroscopic methods including 2D NMR and chiral TLC analyses. Cyclo(dehydrohistidyl-L-tryptophyl) was found to have an inhibitory activity on nitric oxide production with an $IC_{50}$ of $6.5\;{\mu}M$ in activated BV-2 cells. The structure determination and biological activity of cyclo(dehydrohistidyl-L-tryptophyl) was reported for the first time in this study.

• Journal of Pharmaceutical Investigation
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• v.23 no.3
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• pp.133-137
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• 1993

A high-performance liquid chromatographic assay using ion-pair reverse-phase system was developed for the separation of acebutolol and acebutolol acetyl metabolite in plasma. A ion-pair reversephase system consisting of an ODS-bonded silica column and a mixture of 20% $CH_3CN$, 0.1% $H_3PO_4$, 0.035 M heptanesulfonic acid and 0.005 M tetrabutylammonium hydrogen sulfate as the mobile phase were used. Triamterene was employed as an internal standard. Based on 0.2 ml of plasma, the detection limits were 10.4 ng/ml for acebutolol and 10.3 ng/ml of acebutolol acetyl metabolite at the signal-to-noise ratio of 3:1.

• Journal of Food Hygiene and Safety
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• v.17 no.1
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• pp.20-25
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• 2002

This study was aimed to determine the urinary metabolite of profenofos, one of the organophos-phorus pesticides, as the biomarkers of exposure. Urine samples were collected fort 24 hours in metabolic cages after oral administration and dermal application of profenofos to rats. Identification of the derivatized urinary metabolite was determined by GC/MS and excretion time courses of the urinary metabolite was analyzed by GC/MS. Urinary metabolite of profenofos, 4-bromo-2-chlorophenol, was detected in rats urine both after oral administration and dermal application of profenofos. Parent compound was not detected in the experiment. In GC/MS, the mass spectral confirmation for 4-bromo-2-chlorophenol ion was identified at m/z 208.4-bromo-2-chlorophenol was excreted within 48 hours and 72 hours after oral administration and dermal application of profenofos, respectively. In this study, the same urinary metabolite of profenofos was detected both in oral and dermal exposure. Generally, excretion of the urinary metabolite after oral administration was detected faster than after dermal application. It is suggested that urinary 4-bromo-2-chlorophenol could be used as the biomarkers of exposure to profenofos.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.5
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• pp.637-642
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• 2002

Thirty Holstein calves were used to determine effects of age, environment and sex on blood metabolite concentrations during 1 to 90 d of age. Calves were weaned at 75 d of age. Environmental effects are grouped by the difference in month at birth and site of feeding. Blood samples were obtained every 2 or 3 d. The mean metabolite concentration every 3 d was used for the statistical analysis. Dairy bodyweight gain was not affected by environmental group and sex effect. Concentrations of plasma glucose, nonesterified fatty acids (NEFA), triglyceride, total cholesterol and total ketone changed with growth. These developmental changes in metabolite levels would be caused by ruminal maturation with increment of grain intake. Levels of plasma urea nitrogen, glucose, NEFA, triglyceride and total cholesterol drastically changed during a few weeks after birth, indicating that the physiological state in calves greatly changed during that time. Effects of the environmental group and sex were significant in almost all metabolites. Temperature influenced plasma metabolite concentrations. The plasma metabolite concentrations were affected more intensely by heat stress in the infant period than in the neonatal period.

• Journal of Microbiology and Biotechnology
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• v.13 no.1
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• pp.43-49
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• 2003

Metabolism of a new fungicide ethaboxam by soil fungi was studied. Among the fungi tested, Cunninghamelia elegans produced metabolites from ethaboxam, which were not found in the control experiments. M5, a major metabolite from ethaboxam was firmly identified as N-deethylated ethaboxam by LC/MS/MS and NMR. N-Deethylated ethaboxam has been found as a single metabolite in in vitro metabolism with rat liver microsomes. Ml was proved to be 4-ethyl-2-(ethylamino)-1,3-thiazole-5-carboxamide (ETC) by comparing with the authentic compound. In addition, M2, M3, and M4, and M6 were tentatively Identified by LC/MS/MS as hydroxylated and methoxylated ethaboxams, respectively. Production of the major metabolite, N-deethylated ethaboxam, by the fungus suggested that C. elegans would be an efficient eukaryotic microbial candidate for evaluating xenobiotic-driven mammalian risk assessment.

• Analytical Science and Technology
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• v.17 no.4
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• pp.337-346
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• 2004

7-keto-dehydroepiandrosterone-acetate (7-keto-DHEA-acetate) is an anabolic steroids, and we studied basically to the metabolites of it after human dosing. We tested the matrix effect from human urine to detect the 7-keto-DHEA-acetate. And LC/ESI/MS and GC/MSD was used to detect the metabolites in dosed urine. We found the some unknown compound from dosed urine (M1, M2, M3, M4 and M5), and from these results, we supposed that these compounds have the more than 3 hydroxyl and/or ketone group. Metabolite M1 was supposed that molecular weight is 302 and 3-,17-diketone and 7-hydroxyl compound (7-OH-androstendione). Metabolite M2 was supposed that the molecular weight was same to M1 and 7-,17-diketone and 3-hydroxyl compound (7-keto-DHEA).

• Journal of Microbiology and Biotechnology
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• v.30 no.11
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• pp.1697-1705
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• 2020

Meju, a type of fermented soybean paste, is used as a starter in the preparation of various Korean traditional soybean-based foods. In this study, we performed Illumina-MiSeq paired-end sequencing for microbial communities and mass spectrometry analysis for metabolite profiling to investigate the differences between 11 traditional meju products from different regions across Korea. Even though the bacterial and fungal communities showed remarkable variety, major genera including Bacillus, Enterococcus, Variovorax, Pediococcus, Weissella, and Aspergillus were detected in every sample of meju. The metabolite profile patterns of the 11 samples were clustered into two main groups: group I (M1-5) and group II (M6-11). The metabolite analysis indicated a relatively higher amino acid content in group I, while group II exhibited higher isoflavone, soyasaponin, and lysophospholipid contents. The bioactivity analysis proved that the ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)) radical-scavenging activity was higher in group II and the FRAP (ferric reducing antioxidant power) activity was higher in group I. The correlation analysis revealed that the ABTS activity was isoflavonoid, lipid, and soyasaponin related, whereas the FRAP activity was amino acid and flavonoid related. These results suggest that the antioxidant activities of meju are critically influenced by the microbiome and metabolite dynamics.

• YAKHAK HOEJI
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• v.43 no.6
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• pp.834-842
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• 1999

The metabolism and pharmacokinetics of M-l, which is metabolite of pentoxifylline, have been studied in human liver microsomes. Biphasic kinetics was observed from the Eadie-Hofstee plot for the formation of both metabolites of M-l. For the kinetics of pentoxifylline, mean values of $V_{max1}{\;}and{\;}V_{max2}$ were 1,648 and 5,622 nmol/min/mg protein, and the estimated values of $K_{ml}{\;}and{\;}K_{m2}$ were 0.180 and 4.829 mM, respectively. For M-3, mean values of $V_{max1}{\;}and{\;}V_{max2}$ were 0.062 and 0.491 nmol/min/mg protein, and estimated values of $K_{ml}{\;}and{\;}K_{m2}$ were 0.025 and 1.216 mM. The formations of pentoxifylline and M-3 from M-1 were indentified by using several selective inhibitors of cytochrome P450 isoformes at 0.05-5 mM concentration of M-1 in human liver microsomes. For the analysis of low (0.05 mM) concentration of M-1, where the affinity was expected as low, indicated that CYPlA2 and CYP3A4 were major P450 isoforms responsible for pentoxifylline and M-3 formation. CYP3A4 and CYP2A6 appeared to be P450 isoforms responsible for M-3 formation at high (5 mM) concentration of M-1.