• 제목/요약/키워드: Analysis of conjugated metabolites

검색결과 5건 처리시간 0.017초

Selected ion monitoring analysis of conjugated metabolites of methadone using biosynthetic internal standards for the study of methadone-diazepam interaction

  • Kang, Gun-Il
    • Archives of Pharmacal Research
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    • 제6권1호
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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.

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GC-MS를 이용한 소변 중 Diclofenac 및 대사체 분석 (Determination of diclofenac and its metabolites in human urine by GC-MS)

  • 정지혜;허훈;이원웅;홍종기
    • 분석과학
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    • 제21권6호
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    • pp.510-517
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    • 2008
  • 본 연구는 건강한 성인남자로부터 비스테로이드성 항염증제인 diclofenac약물을 복용 후 26시간 동안 배설된 소변을 채취하여 이 약물의 대사과정과 배설에 대하여 연구를 수행하였다. 소변 중에 diclofenac의 포합대사체를 검출하기 위하여 산가수분해 과정을 수행하였고 이 과정에서 diclofenac과 대사체들은 탈수반응에 의해 락탐환이 형성되어 이들의 극성은 산성에서 염기성으로 전환된다. 그러나 변환된 락탐환은 염기조건에서 수산화이온에 의해 쉽게 분해가 일어나므로 오히려 염기성 조건에서의 추출율이 낮아지는 경향이 있어 적정 추출 조건에 대하여 연구하였다. 미량의 대사체 검출을 위하여 trimethylsilylation (TMS) 유도체 반응을 시킨 후 gas chromatograph-mass spectrometer (GC-MS)를 이용하여 분석하였다. 본 연구를 통해 4개의 대사체를 검출할 수 있었으며, 이들은 모두 산화과정에 의해 약물모핵에 hydroxylation된 화합물이었다. 각 대사체는 질량스펙트럼의 해석과 이전 연구결과의 비교를 통하여 구조가 규명되었으며, 이를 바탕으로 시간에 따른 모 약물과 대사체의 배설율을 조사하였다. 본 실험 결과로부터 diclofenac의 체내 대사 경로를 제안하였다.

GC-MS에 의한 소변 중 Ibuprofen의 대사체 규명 및 대사 연구 (Determination of ibuprofen and its metabolites in human urine by GC-MS)

  • 유대형;조정흠;홍종기
    • 분석과학
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    • 제23권2호
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    • pp.179-186
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    • 2010
  • 본 연구는 건강한 성인남자로부터 ibuprofen의 인체 내 대사물질의 규명 및 배설에 대한 연구를 gas chromatography-mass spectrometry (GC/MS) 법으로 수행하였다. Ibuprofen 복용 후 3시간 단위로 15시간까지 소변을 채취하여 실험하였다. 이 중 glucuronide가 포합된 대사체로부터 포합체를 떼어내기 위해 6 M HCl을 통해 $100^{\circ}C$에서 30분 동안 가열하여 산 가수분해 시켰다. 가수분해 된 뇨 중 ibuprofen과 그 대사체를 추출하기 위하여 액체-액체 추출법을 적용하였다. 모약물과 대사체의 추출 최적조건을 찾기 위하여 pH 3, 5 및 8에서 수행하였으며 그 중 pH 3에서 가장 좋은 회수율을 보여 주었다. 또한 미량의 대사체 검출을 위하여 trimethylsilylation (TMS) 유도체 반응을 적용시킨 후 GC-MS를 이용하여 분석하였다. 본 연구에서는 모약물을 포함한 총 5개의 대사체를 검출하였으며, 이들 대사물질들은 주로 산화과정에 의해 약물 모핵에 hydroxylation 또는 carboxylation된 화합물이었다. 또한 시간대별로 채취한 시료에서 각각의 대사체의 배설율의 변화를 관찰함으로써 시간대별 배설율 및 축적률을 구할 수 있었다.

대황목란탕(大黃牧丹湯)의 배오(配伍)분석과 그 약리활성 (Analysis for Compatibility of Daehwangmokdan-tang and Its Pharmacological Activities)

  • 김도회;윤미정;신순식
    • 대한한의학방제학회지
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    • 제26권1호
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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.

Development of succinate producing Cellulomonas flavigena mutants with deleted succinate dehydrogenase gene

  • Lee, Heon-Hak;Jeon, Min-Ki;Yoon, Min-Ho
    • 농업과학연구
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    • 제44권1호
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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.