• Title/Summary/Keyword: reaction phase

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Bioequivalence Study of Toriem® Tablet to Motilium-M® Tablet (Domperidone Maleate 12.72 mg) Evaluated by Liquid Chromatography/Tandem Mass Spectrometry

  • Ryu, Ju-Hee;Choi, Sang-Jun;Lee, Myung-Jae;Lee, Jin-Sung;Kang, Jong-Min;Tak, Sung-Kwon;Seo, Ji-Hyung;Lee, Kyung-Tae
    • Journal of Pharmaceutical Investigation
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    • v.39 no.1
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    • pp.65-71
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    • 2009
  • The aim of the present study was to evaluate the bioequivalence of two domperidone maleate tablets, Motilium-$M^{(R)}$ Tablet (Janssen Korea Ltd., reference product) and $Toriem^{(R)}$ Tablet (Daewon Pharm. Co., Ltd., test product). Domperidone was extracted by liquid-liquid extraction using tert-butyl methyl ether and separated in less than 3 min on $C_{18}$ reverse-phase column using an isocratic elution. A tandem mass spectrometer, as detector, was used for quantitative analysis in positive mode by a multiple reaction monitoring mode to monitor the m/z $426.1{\rightarrow}119.1$ and the m/z $837.4{\rightarrow}158.2$ transitions for domperidone and the internal standard (roxithromycin), respectively. Calibration curves, from $0.05{\sim}50$ ng/mL of domperidone, showed correlation coefficients (r) higher than 0.9941. Intra day and inter day precision (C.V. %) for quality control were ranged from 10.04 to 16.09% and from 10.87 to 18.69%, respectively. The lower limit of quantification (LLOQ) of domperidone was 0.05 ng/mL. The method described is precise and sensitive and has been successfully applied to the study of bioequivalence of domperidone in 24 healthy Korean volunteers. Twenty-four healthy male Korean volunteers received a single dose of each medicine ($2{\times}12.72\;mg$ domperidone maleate) in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of domperidone were monitored for over a period of 24 hr after the administration. $AUC_{0-t}$ (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. The 90% confidence intervals for the log transformed data were within acceptable range of log 0.8 to log 1.25 (e.g., $log\;0.92{\sim}log\;1.05$ for $AUC_{0-t}$, $log\;0.81{\sim}log\;1.05$ for $C_{max}$). The major parameters, $AUC_{0-t}$ and $C_{max}$ met the criteria of KFDA for bioequivalence indicating that $Toriem^{(R)}$ tablet is bioequivalent to Motilium-$M^{(R)}$ tablet.

Development of LC-MS/MS Quantitation Method for Ethoxyquin in Fishery Products (수산물 중 에톡시퀸의 LC-MS/MS 정량분석법 개발)

  • Shin, Dasom;Chae, Young-Sik;Kang, Hui-Seung;Lee, Soo-Bin;Cho, Yoon-Jae;Cheon, So-Young;Jeong, Jiyoon;Rhee, Gyu-Seek
    • Journal of Food Hygiene and Safety
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    • v.31 no.6
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    • pp.432-438
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    • 2016
  • Ethoxyquin (EQ, 1,2-dihydro-6-ethoxy-2,2,4-trimethyl-quinoline) is quinoline-based antioxidant used in the animal feed and food industry to protect the raw materials and final products against oxidation. In recent years the use of synthetic antioxidants in fishmeal ingredients carry-over to farmed fish fillets has received increasing attention in food safety. This study was conducted to develop an analytical method to determine EQ in aquatic products. The analytes were confirmed and quantified via liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the positive ion mode using multiple reaction monitoring (MRM). The sample was extracted with 1 N HCl (in case of flatfish extracted with 1 N HCl containing 10% acetonitrile). Then, solid phase extraction (SPE) was used for the cleanup. Standard calibration curves presented linearity with the correlation coefficient ($r^2$) > 0.99, analyzed at 0.005-0.2 mg/kg concentration. The developed method was validated according to the Codex Alimentarius Commission (CAC) guideline. The limits of quantitation for EQ were 0.01 mg/kg. Average recoveries ranged from 81.3% to 107%. The repeatability of measurements, expressed as the coefficient of variation (CV, %), was below 10%. The analytical method was characterized with high accuracy and acceptable sensitivity to meet CODEX guideline requirements and would be applicable to analyze the EQ residue in aquatic products.

Behavior of trace metals in Masan Bay, Korea during oxygen deficient period (하계 마산만 혐기성 환경에서의 미량금속의 거동)

  • Jin Y.H.;Kim K.T.;Chung C.S.;Kim S.H.;Yang D.B.;Hong G.H.;Lee K.W.
    • Journal of the Korean Society for Marine Environment & Energy
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    • v.3 no.4
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    • pp.56-64
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    • 2000
  • Behavior of trace metals in Masan Bay, Korea was studied in August 1998 when the oxygen deficient condition occurred. Dissolved Cd and Zn concentration in the surface waters decreased with increasing distance from Masan Harbor. Dissolved concentrations of Cd, Cu Pb and Zn in the surface waters were higher than bottom waters. Particulate(acid-teachable fraction) concentrations of Cu, Cd and Pb in the surface waters of Masan Bay decreased with increasing distance from Masan Harbor. Bottom waters contained higher concentrations of particulate Cd, Cu, Pb and Zn than surface waters. Distribution coefficients between dissolved and particulate phase (K/sub d/) of Cu and Cd decreased with the increasing distance from the Harbor, possibly due to reaction of these elements with sewage-derived particulate matter Al, Zn, Cu, Cd, and Pb in the surface sediment showed relatively high concentration in the inner Masan Bay.

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Tumorigenic Effects of Endocrine-disrupting Chemicals are Alleviated by Licorice (Glycyrrhiza glabra) Root Extract through Suppression of AhR Expression in Mammalian Cells

  • Chu, Xiao Ting;de la Cruz, Joseph;Hwang, Seong Gu;Hong, Heeok
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4809-4813
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    • 2014
  • Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a representative EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells, used as a tumor model, were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, $400{\mu}g/mL$) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. The expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, was also down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analysis also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated diseases.

Validation of an LC/MS/MS Method for the Pharmacokinetic Study of Lercanidipine (염산레르카니디핀 체내동태 연구를 위한 혈청 중 레르카니디핀의 LC/MS/MS 정량법 검증)

  • Kim, Se-Mi;Kim, Hwan-Ho;Shin, Sae-Byeok;Kang, Hyun-Ah;Yoon, Hwa;Cho, Hea-Young;Kim, Yoon-Gyoon;Yang, Chan-Woo;Yong, Chul-Soon;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.37 no.4
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    • pp.223-227
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    • 2007
  • A rapid, simple and sensitive LC/MS/MS method for the determination of lercanidipine in human serum was validated and applied to the pharmacokinetic study of lercanidipine. Lercanidipine and internal standard, amlodipine, were extracted from human serum by liquid-liquid extraction with hexan-isoamyl alcohol (100: 1, v/v) and analyzed on a $Symmetry^{(R)}$ MS $C_{18}$ column with the mobile phase of acetonitrile-0.2% aqueous formic acid (70: 30, v/v). Using MS/MS with multiple reaction monitoring (MRM) mode, lercanidipine and amlodipine were detected without severe interferences from human serum matrix. Lercanidipine produced a protonated precursor ion ($[M+H]^+$) at m/z 612.3 and a corresponding product ion at m/z 280.0. Internal standard produced a protonated precursor ion ($[M+H]^+$]) at m/z 409.0 and a corresponding product ion at m/z 238.0. The ruggedness of this method was investigated using quality control (QC) samples. This method showed linear response over the concentration range of 0.05-20 ng/mL with correlation coefficient greater than 0.999. The lower limit of quantitation using 0.5 mL of serum was 0.05 ng/mL, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the developed method ranged from 85.51 to 112.2% for lercanidipine with overall precision (% C.V.) being 3.56-13.1%. This method showed good ruggedness (within 15% C.V.) and was successfully applied for the analysis of lercanidipine in human serum samples for the pharmacokinetic studies, demonstrating the suitability of the method.

Study on the Physical Properties of Alkoxysilane-based Stone Consolidants with Different Hydrolysis (알콕시 실란계 석조문화재 강화제의 가수 분해도에 따른 특성 연구)

  • Park, Soung-Jin;Won, Jong-Ok;Kim, Jeong-Jin;Do, Jin-Young;Kim, Sa-Dug
    • Journal of Conservation Science
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    • v.27 no.2
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    • pp.201-209
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    • 2011
  • While consolidants based on tetraethoxysilane (TEOS) have been widely used for the consolidation of decaying stone heritages, TEOS-based consolidants suffer from practical drawbacks, such as crack formation of the gel during the drying phase due to the developed capillary force. We have prepared new TEOS-based consolidants containing flexible (3-glycidoxypropyl) trimethoxysilane (GPTMS) in order to reduce capillary force development during gel drying. In this study, we have prepared TEOS/GPTMS-based consolidants containing ETEOS in order to improve the surface hydrophobisity. The physical properties of the TEOS/GPTMS/ETEOS solution with different hydrolysis were compared with those of the commercial products Wacker OH$^{(R)}$. The contact angle of the surface increased with the addition of the ETEOS, which is higher than that of Wacker OH$^{(R)}$. The sol-gel mechanism was manipulated by the degree of hydrolysis as well as the amount of ETEOS. The properties and the applicability of the developed consolidants for the decayed Korean granites are also investigated.

Reductive stripping of Np using a n-butyraldehyde from a loaded TBP phase containing Np (Np 함유 TBP 유기상으로부터 NBA에 의한 Np의 환원 역추출)

  • Lee, Eil-Hee;Lim, Jae-Kwan;Chung, Dong-Yong;Yang, Han-Beom;Kim, Kwang-Wook
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.6 no.3
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    • pp.163-170
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    • 2008
  • The reductive stripping of Np using a n-butyraldehyde (NBA) from loaded organic solution containing Np, which was oxidative-extracted in a system of a 30 % TBP/NDD-2M $HNO_3$ and O/A=2 containing 0.005 M $K_2Cr_2O_7$ as an oxidant of Np, was studied. The stripping yields of Np was increased with an increasing the NBA concentration, with a decreasing the nitric acid concentration of stripping solution and with a decreasing the reaction temperature. The apparent reductive stripping rate equation was shown by the following equation : $-d[Np]_{Org.}/dt$ = 1,524 exp(-2,906/T) $[NBA]^{0.91}\;[H^+]^{-0.92}[Np]_{Org.}$. At 1.04 M NBA and 2 M $NHO_3$, the stripping yield of Np and U was 70.1 %, and 7.1 %, respectively, and the separation factor of U over Np ($=D_U/D_{Mp}$) was about 30.4. Therefore, it was found that U and Np co-extracted in a system of TBP-$HNO_3$ could be effectively mutual-separated by the NBA.

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Catalytic Characteristics of Mn-PC for VOCs Combustion (VOCs 연소용 Mn-PC 촉매 특성)

  • Seo, Seong-Gyu;Ma, Zhong-Kun;Liu, Yi;Yoon, Hyung-Sun;Kim, Sang-Chai
    • Journal of Korean Society of Environmental Engineers
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    • v.33 no.4
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    • pp.237-242
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    • 2011
  • In this study, the catalytic activity of Mn-Phthalocyanine (Mn-PC) for VOCs (acetadehyde, propionaldehyde and toluene) combustion was determined. The reaction was carried out in a fixed bed reactor at the temperature range of $200{\sim}380^{\circ}C$. We investigated the physicochemical properties of Mn-PC before and after the pretreatment (air, $450^{\circ}C$, 1 hr, 60 cc/min) by TGA (Thermogravimetric Analyzer), BET (Brunauer Emmett Teller), EA (Elemental Analyzer), XRD (X-ray Diffractometer) and SEM (Scanning Electronic Microscope). By TGA analysis, 88 wt.% mass loss of Mn-PC was found at $419^{\circ}C$. The BET surface area of Mn-PC increased after the pretreatment. The decomposition and combustion of organic components in Mn-PC were observed by EA analysis. We also confirmed that Mn-PC had transformed into a new manganese oxide phase ($Mn_3O_4$) after the pretreatment by XRD analysis. By SEM analysis, many of the micropores generated during the pretreatment were found. The catalytic activity of Mn-PC with the pretreatment for propionaldehyde combustion was higher than that of $Mn_3O_4$ and fresh Mn-PC. It showed the catalytic activity of Mn-PC with the pretreatment for VOCs combustion by the order of toluene < acetadehyde < propionaldehyde.

Synthesis and Small Animal Brain PET Study of a Serotonin Receptor Radiotracer, 18F-Mefway (세로토닌 5-HT1A수용체 방사성 추적자 18F-Mefway의 합성과 소동물 뇌 PET 연구)

  • Ahn, Sung-Min;Hong, Tae-Kee;Ryu, Young-Hoon;Choi, Jae-Yong;Kim, Sung-Chul
    • The Journal of the Korea Contents Association
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    • v.9 no.11
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    • pp.262-270
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    • 2009
  • $^{18}F$-mefway has been developed as radioligand for serotonin receptor 5-$HT_{1A}$. The object of this study was to obtain the mefway precursor with the higher yield than previous method and to identify whether $^{18}F$-mefway can bind to 5-$HT_{1A}$ or not. from microPET imaging of small animal brain. Precursor was prepared by a modification of the reported procedure then [$^{18}F$] labeling was performed by adding $^{18}F$ ion at $130^{\circ}C$ in the hot cell for 30min. After purification of reaction mixture using alumina Sep-pak and HPLC, microPET images of small animal brain were determined. The chemical yield of precursor was increased from 9% to 34% using oxalyl chloride and LAH/diethylether. We synthesized a precursor which was successfully labeled with no-carrier-added $^{18}F$-by new synthetic route. This research suggest that $^{18}F$-mefway will be used a radiopharmaceutical for evaluation of central nerve system disorder as imaging a gent for 5-$HT_{1A}$ receptor.

Detection of Differentially Expressed Genes in Glioblastoma by Suppression Subtractive Hybridization

  • Yu, Na-Mi;Ahn, Jung-Yong;Choi, Eun-Jin;Hong, Yong-Kil;Kim, Tai-Gyu;Kim, Chang-Hyun;Lee, Kyu-Sung;Kim, Dong-Seok;Kim, Jin-Kyeoung
    • Journal of Korean Neurosurgical Society
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    • v.37 no.6
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    • pp.443-448
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    • 2005
  • Objective: A variety of genetic alterations in human glioblastoma comprises signal transduction and cell cycle arrest control of cellular processes. Subtractive hybridization is potentially a faster method for identifying differentially expressed genes associated with a particular disease state. Using the technique of subtraction, we isolated novel genes that are overexpressed in glioblastoma tissue as compared to normal brain tissue. Methods: We evaluated the differential expression of genes in each of hybridizing tester and driver cDNAs to digested 130 clones. After sequencing of 130 clones and homology search, this study performed to determine mRNA expression of the unknown gene, "clone 47", in brain tissue, glioblasoma, and several cancer cell lines by reverse transcription-polymerase chain reaction (RT-PCR). To test the time course for Go-phase arrest, serum stimulation and expression at various times for RT-PCR performed. Results: We identified 23 novel genes by BLAST of the digested 130 clones. The expressions of "clone 47" mRNA of glioblastoma and several cancer lines were significantly higher than normal brain tissues and several normal cell lines. We confirmed the mRNA expression of "clone 47" was up-regulation for $0.5{\sim}1hr$ of WI-38 cell differentiation. Conclusion: The novel gene, "Clone 47" is upregulated in glioblastoma tissue and several cancer cell lines. This gene is time dependent activation during time course of serum stimulation. This result suggests that "clone 47" playa role in brain tumorigenesis and the activation of this "clone 47" may be necessary for the development of cancer.