• Archives of Pharmacal Research
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• v.6 no.1
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• pp.7-16
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• 1983

A methadone-diazepam interaction study in rats was performed in which conjugated metabolites of methadone were analyzed using deuterated biosynthetic internal standards. Diazepam (5mg/kg) was given to rats through a cannulate djugular vein and a subcutaneous dose of methadone (10mg/kg) was given. Bile was collecte through the cannulate dbile duct over a period of 24 hours. The deuterium label of the internal standards was found to be stable under conditions of the prolonged incubation. There was no significant difference in the excretion of the metabolites between the control and the diazepam treated rats. Feasibility of using biosynthetic internal standards with selected ion monitoring was established for the drug metabolism and kinetic studies.

• Analytical Science and Technology
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• v.21 no.6
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• pp.510-517
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• 2008

This study has been described the metabolism and excretion in a healthy male urine collected for 26hrs after oral administration of diclofenac. To detect conjugated metabolites of diclofenac, urine sample was acid-hydrolyzed under the conditions of 6M-HCl at over $110^{\circ}C$ for 1hr. During the acidic hydrolysis process, diclofenac and its metabolites were converted into their corresponding lactam-ring through dehydration reaction. As results of chemical conversion by means of hydrolysis, the structures of diclofenac and its metabolites were also changed acidic to basic forms. However, lactam-ring was degraded by hydroxyl ion at basic condition. Thus, the extraction rate of dehydrated diclofenac and its metabolites was not favored at basic condition. For the determination of trace amounts of diclofenac and its metabolites in urine, trimethylsilylation (TMS) with MSTFA was applied and followed by analysis with gas chromatograph-mass spectrometer. In this study, four metabolites that are formed by the hydroxylation of parent drug were mainly detected. Each metabolite was tentatively identified by both interpretation of mass spectra and comparison with previously reported results. In addition, time profile of urinary excretion rate for parent drugs and metabolites was studied. Finally, the metabolic pathway of diclofenac was suggested on the basis of the elucidation of its metabolites and excretion profiles.

• Analytical Science and Technology
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• v.23 no.2
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• pp.179-186
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• 2010

The oxidative metabolism of ibuprofen in healthy male urine collected at 3, 6, 9, 12 and 15 h after oral administration of ibuprofen was studied by GC/MS assay. To detect conjugated metabolites of ibuprofen, urine sample was acid-hydrolyzed with 6 M HCl at $100^{\circ}C$ for 30 min. To effectively extract ibuprofen and its metabolites, liquid-liquid extraction (LLE) was conducted at pH 3, 5, and 7, respectively. As a result, LLE at pH 3 was shown to be the best extraction condition. For the determination of trace amounts of ibuprofen and its metabolites in extract, trimethylsilylation (TMS) with BSTFA was applied and followed by GC/MS analysis. In this study, main 5 metabolites including parent drug were detected and these metabolites were assigned as three hydroxylated forms and one carboxylated form. Each metabolite was tentatively identified by both interpretation of mass spectrum and comparison with previously reported results. In addition, time profile of urinary excretion rate for parent drugs and metabolites was studied. Finally, the metabolic pathways of ibuprofen were suggested on the basis of the structural elucidation of its metabolites and excretion profiles.

• Herbal Formula Science
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• v.26 no.1
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• pp.81-102
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• 2018

Objectives : I analysed daehwangmokdan-tang's compatibility principle by the system of chief, deputy, assistant, and envoy and investigated pharmacological activities by categorizing with chemical components, molecular level, cellular level, animal level and human level based on Korean and Chinese studies for this formula. Methods : Daehwangmokdan-tang's compatibiltity principle was examined by the system of chief, deputy, assistant, and envoy. I looked into studies that presented in Korea from 1956 to 2016 about daehwangmokdan-tang through KOREA INSTITUTE OF ORIENTAL MEDICINE, Korean medicine information system (OASIS) and in Chinese for 20 years about daehwangmokdan-tang through China National Knowledge Infrastructure, CNKI. Then classify into chemical components, molecular level, cellular level, animal level and human level to analyse. Results : According to the system of chief, deputy, assistant, and envoy, chief herb is Rhei Radix et Rhizoma and Moutan Cortex, deputy herb is Natrii Sulfas and Persicae Semen, assistant and envoy herbs are Trichosanthis Semen. The amount of extraction of paeonol, total anthraquinone, and conjugated anthraquinone from daehwangmokdan-tang with the formulation of the system of chief, deputy, assistant, and envoy was the highest, and in the formulation of chief herb and deputy herb, the extraction amount of paeonol and conjugated anthraquinone was the lowest. With other formulations, the amount of extraction of total anthraquinone and conjugated anthraquinone was improved, although the degree was different. In particular, when it is blended with Persicae Semen as a deputy herb, the extraction amount of total anthraquinone and conjugated anthraquinone of Rhei Radix et Rhizoma as a chief herb is greatly increased, and the extraction amount of paeonol is rather different, but it is lowered. It was found that the amount of Mg Ca K Na in daehwangmokdan-tang was the highest. Pharmacological activities can be detected in inflammatory mediators and enzymes for molecular level. For cellular level, it can be determined in lipopolysaccharide (LPS)-stimulated RAW 264.7 cell line. In mouse and rats for animal level and human level, in inflammatory diseases (acute appendicitis, acute pancreatitis, acute cholecystitis, acute abdominal disease, ect.), pharmacological activities was caught. Conclusions : From the above results, daehwangmokdan-tang is composed in line with the system of chief, deputy, assistant, and envoy, suggesting that there is certain rationality and scientific. Pharmacological activities of daehwangmokdan-tang are effective to anti-inflammation, improvement of sepsis, analgesic, muscle relaxation, and improvement of intestinal flora and its metabolites. Daehwangmokdan-tang is consistent with the action of diuresis and anti-inflammation in terms of the content of elements, suggesting that there is action of purging fire and removing blood stasis, defecation detoxification, cooling blood and clearing heat and activating blood and dispersing stasis.

• Korean Journal of Agricultural Science
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• v.44 no.1
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• pp.30-39
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• 2017

This study was performed to produce succinic acid from biomass by developing mutants of Cellulomonas flavigena in which the succinate dehydrogenase gene (sdh) is deleted. For development of succinate producing mutants, the upstream and downstream regions of sdh gene from C. flavigena and antibiotic resistance gene (neo, bla) were inserted into pKC1139, and the recombinant plasmids were transformed into Escherichia coli ET12567/pUZ8002 which is a donor strain for conjugation. C. flavigena was conjugated with the transformed E. coli ET12567/pUZ8002 to induce the deletion of sdh in chromosome of this bacteria by double-crossover recombination. Two mutants (C. flavigena H-1 and H-2), in which sdh gene was deleted in the chromosome, were constructed and confirmed by PCR. To estimate the production of succinic acid by the two mutants when the culture broth was fermented with biomass such as CMC, xylan, locust gum, and rapeseed straw; the culture broth was analyzed by HPLC analysis. The succinic acid in the culture broth was not detected as a fermentation products of all biomass. One of the reasons for this may be the conversion of succinic acid to fumaric acid by sdh genes (Cfla_1014 - Cfla_1017 or Cfla_1916 - Cfla_1918) which remained in the chromosomal DNA of C. flavigena H-1 and H-2. The other reason could be the conversion of succinyl-CoA to other metabolites by enzymes related to the bypass pathway of TCA cycle.