• 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.

• Journal of Microbiology and Biotechnology
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• v.18 no.10
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• pp.1659-1662
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• 2008

Pseudomonas chlororaphis O6 exhibits induced systemic resistance (ISR) against P. syringae pv. tabaci in tobacco. To identify one of the ISR metabolites, O6 cultures were extracted with organic solvents, and the organic extracts were subjected to column chromatography followed by spectroscopy analyses. The ISR bioassay-guided fractionation was carried out for isolation of the metabolite. High-resolution mass spectrometric analysis of the metabolite found $C_{9}H_{9}O_{3}N$ with an exact mass of 179.0582. LC/MS analysis in positive mode showed an $(M+H)^{+}$ peak at m/z 180. Nuclear magnetic resonance ($^{1}H,\;^{13}C$) analyses identified all protons and carbons of the metabolite. Based on the spectroscopy data, the metabolite was identified as 4-(aminocarbonyl) phenylacetate (4-ACPA). 4-ACPA applied at 68.0 mM exhibited ISR activity at a level similar to 1.0 mM salicylic acid. This is the first report to identify an ISR metabolite produced by P. chlororaphis O6 against the wildfire pathogen P. syringae pv. tabaci in tobacco.

• 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 Environmental Health Sciences
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• v.28 no.1
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• pp.67-77
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• 2002

This study was aimed to determine the urinary metabolite of IBP, one of the organophosphorus pesticides, as the biomarkers of exposure. Urine samples were collected for 24 hours in metabolic cages after oral administration and dermal application of IBP 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/FPD. Urinary metabolite o IBP, diisopropyl phosphorothioate, was detected in rats urine both after oral administration and dermal application of IBP. Parent compound was not detected in the experiment. In GC/MS, the mass spectral confirmation for diisopropyl phosphorothioate ion was identified at m/z 254. Diisopropyl phosphorothioate was excreted within 48 hours and 72 hours after oral administration and dermal application of IBP, respectively. In this study, the same urinary metabolite of IBP was detected both in oral and dermal exposure. Generally, excretion of the urinary metabolite after oral administration was faster than after dermal application. It is suggested that urinary diisopropyl phosphorothioate could be used as the biomarkers of exposure to IBP.

• 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).

• 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.

• 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.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.402.1-402.1
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• 2002

The LC/MS/MS method for the simultaneous determination of sildenafil and its active metabolite N-demethylsildenafil in human plama was developed. Sildenafil. its active metabolite and the internal standard. DA-8159 were extracted form human plasma by liquid-liquid partitioning. A reverse-phase HPLC separation was performed on Luna phenylhexyl column with the mixture of acetonitrile-5 mM ammonium formate (55:45. v/v) as mobile phase. (omitted)

• 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.

• Journal of Ginseng Research
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• v.37 no.4
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• pp.451-456
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• 2013

Compound K is a major metabolite of ginsenoside Rb1, which has various pharmacological activities in vivo and in vitro. However, previous studies have focused on the pharmacokinetics of a single metabolite or the parent compound and have not described the pharmacokinetics of both compounds in humans. To investigate the pharmacokinetics of ginsenoside Rb1 and compound K, we performed an open-label, single-oral dose pharmacokinetic study using Korean Red Ginseng extract. We enrolled 10 healthy Korean male volunteers in this study. Serial blood samples were collected during 36 h after Korean Red Ginseng extract administration to determine plasma concentrations of ginsenoside Rb1 and compound K. The mean maximum plasma concentration of compound K was $8.35{\pm}3.19$ ng/mL, which was significantly higher than that of ginsenoside Rb1 ($3.94{\pm}1.97$ ng/mL). The half-life of compound K was 7 times shorter than that of ginsenoside Rb1. These results suggest that the pharmacokinetics, especially absorption, of compound K are not influenced by the pharmacokinetics of its parent compound, except the time to reach the maximum plasma concentration The delayed absorption of compound K support the evidence that the intestinal microflora play an important role in the transformation of ginsenoside Rb1 to compound K.