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Full validation of high-throughput bioanalytical method for the new drug in plasma by LC-MS/MS and its applicability to toxicokinetic analysis

  • Han, Sang-Beom
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2006.11a
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    • pp.65-74
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    • 2006
  • Modem drug discovery requires rapid pharmacokinetic evaluation of chemically diverse compounds for early candidate selection. This demands the development of analytical methods that offer high-throughput of samples. Naturally, liquid chromatography / tandem mass spectrometry (LC-MS/MS) is choice of the analytical method because of its superior sensitivity and selectivity. As a result of the short analysis time(typically 3-5min) by LC-MS/MS, sample preparation has become the rate- determining step in the whole analytical cycle. Consequently tremendous efforts are being made to speed up and automate this step. In a typical automated 96-well SPE(solid-phase extraction) procedure, plasma samples are transferred to the 96-well SPE plate, internal standard and aqueous buffer solutions are added and then vacuum is applied using the robotic liquid handling system. It takes only 20-90 min to process 96 samples by automated SPE and the analyst is physically occupied for only approximately 10 min. Recently, the ultra-high flow rate liquid chromatography (turbulent-flow chromatography)has sparked a huge interest for rapid and direct quantitation of drugs in plasma. There is no sample preparation except for sample aliquotting, internal standard addition and centrifugation. This type of analysis is achieved by using a small diameter column with a large particle size(30-5O ${\mu}$m) and a high flow rate, typically between 3-5 ml/min. Silica-based monolithic HPLC columns contain a novel chromatographic support in which the traditional particulate packing has been replaced with a single, continuous network (monolith) of pcrous silica. The main advantage of such a network is decreased backpressure due to macropores (2 ${\mu}$m) throughout the network. This allows high flow rates, and hence fast analyses that are unattainable with traditional particulate columns. The reduction of particle diameter in HPLC results in increased column efficiency. use of small particles (<2 urn), however, requires p.essu.es beyond the traditional 6,000 psi of conventional pumping devices. Instrumental development in recent years has resulted in pumping devices capable of handling the requirements of columns packed with small particles. The staggered parallel HPLC system consists of four fully independent binary HPLC pumps, a modified auto sampler, and a series of switching and selector valves all controlled by a single computer program. The system improves sample throughput without sacrificing chromatographic separation or data quality. Sample throughput can be increased nearly four-fold without requiring significant changes in current analytical procedures. The process of Bioanalytical Method Validation is required by the FDA to assess and verify the performance of a chronlatographic method prior to its application in sample analysis. The validation should address the selectivity, linearity, accuracy, precision and stability of the method. This presentation will provide all overview of the work required to accomplish a full validation and show how a chromatographic method is suitable for toxirokinetic sample analysis. A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method developed to quantitate drug levels in dog plasma will be used as an example of tile process.

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Analysis of the particulate matters in the vertical-flow woodchip wetland treating stormwater from paved road (포장도로 강우유출수 처리목적의 수직흐름형 우드칩 충진 습지에서 입자상 물질분석)

  • Yuan, Qingke;Kim, Youngchul
    • Journal of Wetlands Research
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    • v.20 no.2
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    • pp.145-154
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    • 2018
  • In this study, three pilot-scale wetland systems were built for treating stormwater runoff from asphalt road. Each of the system consists of a settling tank and a vertical flow wetland packed with 25%, 50%, and 75% woodchip as treatment media. According to the analysis of the distributions of particle size, it was found that solids ranging in size $0.52-30{\mu}m$ were predominant in the stormwater runoff. After 24-hours settling, those coarser than $20{\mu}m$ were significantly detained. Further retention, especially for the finer-sized fraction, occurred in the wetland through internal recirculation during the dry day periods. As a primary media of the wetland, woodchip showed a high filtration and attachment capacity for the particulates in pre-settled stormwater, whereas overall amount of solids in the wetland effluent increased due to the detachment of woody elements from the media. This was observed mainly during the initial 75 days of operation, and the size and detachment rate were found to be strongly related with the woodchip packing ratio. The mechanism involving woody particle detachment was modeled as a first-order form. In addition, water quality factors and operational parameters affecting the detachment were analyzed and discussed.

Changes of freshness in Pleurotus eryngii according to oxygen permeability of packaging film and net weight (포장재 산소투과도 및 포장량에 따른 큰느타리버섯 신선도 변화)

  • Lee, Yun-Hae;Jeoung, Yun-Kyeoung;Baek, Il-Sun;Lee, Han-Bum;Chi, Jeong-Hyun;Jhune, Chang-Sung
    • Journal of Mushroom
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    • v.11 no.4
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    • pp.292-296
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    • 2013
  • Recently, Pleurotus eryngii, King oyster mushroom is the main export item in South Korea mushroom industry. For appropriate transportation to Europe and USA markets, it is necessary to elucidate suitable conditions of storage and treatment of post-harvest during long time shipping. Whole mushrooms were packed with polypropylene anti-fog film (30 um) without trimming. The range of package weight and oxygen permeability of film were 200 g~400 g and 2000~5000 $cc/m^2$, 24 h,atm, respectively. The weight loss ratio was increased with increasing storage time. There were no big differences in weight loss ratio according to package weight and oxygen permeability of film at low temperature storage($4^{\circ}C$). In case of package weight is 400 g and oxygen permeability of film is 3000 $cc/m^2$, 24 h, atm. As a results of freshness, the optimum packing weight and oxygen permeability of film of P. eryngii were 400 g and below 2,000 $cc/m^2$, 24 h, atm, respectively.

The Manufacturing of Low-fat Hamburger Patties Added Organic Vegetable (친환경 유기농 채소가 첨가된 저지방 햄버거 패티의 제조)

  • Chung, Ku-Young;Chung, Eui-Ryung;Lee, Joo-Yeon
    • Food Science of Animal Resources
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    • v.28 no.2
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    • pp.165-170
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    • 2008
  • In this study, the physicochemical, microbial, and sensory properties of law-fat hamburger patties during storage for 25 days at $7{\pm}1^{\circ}C$ were investigated. The law-fat hamburger patties were manufactured by three different packing methods (control: added with 10% lard regular-fat patty, T1: added with 10% lard and organic vegetable of regular-fat patty, T2: added with 3% olive oil of vegetability low-fat patty, T3: added with 3% lard of low-fat patty). The pH of all treated samples increased as the storage time increased, and then decreased after 15 days of storage. The low-fat hamburger patty added with organic olive oil (T2) showed significantly higher pH (p<0.05) compared with other treatments (T1 and T3). The TBARS values of the all treated samples tended to increase after 5 days of storage, and then significant quality loss was observed after 15 days of storage period for the control (T1). However, the samples of the vegitability low-fat patty added organic olive oil had longer shelf-life than the control. The total bacterial counts were 7 log CFU/g after 15 days and 20 days of storage for the control and treatments, respectively. The results of this study showed that the storage period of the treatments was slightly extended compared with the control. Low-fat hamburger patties showed no differences for overall acceptability between control and other patties.

Synthesis and Structural Analysis of Binary Alloy ($MoRu_3$, $MoRh_3$) (이성분계 금속합금($MoRu_3$, $MoRh_3$)의 합성 및 구조분석)

  • Park, Yong Joon;Lee, Jong-Gyu;Kim, Jong Goo;Kim, Jung Suk;Jee, Kwang-Yong
    • Analytical Science and Technology
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    • v.11 no.3
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    • pp.189-193
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    • 1998
  • Binary alloys, $MoRu_3$ and $MoRh_3$, have been prepared using arc melting furnace. Mo and the noble metals Ru and Rh are the constituents of metallic insoluble residues, which were found in the early days of the post-irradiation studies on uranium oxide fuels. Detailed structural informations about these alloys have not been reported on JCPDS files of ICDD (International Centre for Diffraction Data). The results of X-ray diffraction study showed that the alloy was crystallized in hexagonal close-packing, well known as ${\varepsilon}$-phase. The X-ray diffraction patterns of these alloys matched well to that of $WRh_3$ with $P6_3/mmc$ of space group. The lattice parameters, a and c, were calculated using the least squares extrapolation. It was found from X-ray photoelectron spectroscopic measurements that Mo on the surface of the alloy was oxidized to Mo(6+), which could be removed by sputtering with Ar ions for approximately 15 minutes. The changes in binding energy of Mo, Ru, and Rh on the surface of the alloy were not observed. Magnetic susceptibility measurements resulted in the typical Pauli-paramagnetic behavior in the temperature range of 2 to 300 K.

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Effect of TiCN/WC Ratio on Grain Shape and Grain Growth in the TiCN-WC-Co System (TiCN-WC-Co 계에서 TiCN/WC 비의 변화에 따른 입자모양과 입자 성장)

  • 이보아;강석중;윤덕용;김병기
    • Proceedings of the Korean Powder Metallurgy Institute Conference
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    • 2002.11a
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    • pp.29-29
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    • 2002
  • 공구강 등 산업용 재료로 널리 사용되는 카바이드 계 재료는 입자 크기 및 분포에 따라 기계적 성질이 변화하므로, 이를 제어하고 조절하는 기술에 관하여 많은 연구가 진행되어 왔다. 본 연구에서는 TiCN-WC-Co 복합초경계 에서 소결 공정 및 조성변화에 따른 입자 모양을 관찰하고 이에 따른 업자 성장 거동을 고찰하였다. 일반적으로 입자 조대화 양상과 고상 입자의 모양과는 밀접한 관계가 있다. 각진 입자의 경우에 는 계면이 원자적으로 singular 하여 원자의 홉착이 어렵기 때문에 임계값 이상의 성장 구동력을 받 는 몇몇 입자만 성장하는 비정상 입자 성장이 일어날 수 있다. 반면에 계면이 rough한 퉁큰 엽자의 경우에는 원자 홉착에 필요한 구동력이 존재하지 않아 성장 구동력을 받는 모든 입자들이 성장하기 때문에 정상 입자 성장을 하게 된다. 이와 같이 입자 모양에 따른 입자 성장 거동은 전체 미세구조를 결정하게 되며, 이에 따른 물리 화학적 물성을 변화시킨다. 이러한 입자 성장 원리를 적용하 면 복합초경계 (TiCN-WC-Co)에서도 입자성장이 억제되고 치밀한 소결체를 제조할 수 있을 것이다. 본 실험에서는 평균입도가 각각 0.1, 1.33, 2$\mu\textrm{m}$인 TiCN, WC, Co 분말을 사용하여 $((I00_{-x)}TiCN+_xWC)-30Co$ (wt%) 조성에서 TiCN/WC 비를 변화시키면서 업자 모양과 입자성장 거동을 관찰하였다. 청량된 분말은 WC 초경 볼로 밀렁하고, 건조한 후, 100 mesh 체로 조립화 하였다. 이 분말을 100 MPa의 압력으로 냉간정수압성형 하고 $10^{-2}$ torr의 진공분위기의 graphite f furnace에서 carbon black으로 packing 하여 액상형성 온도 이상에서 소결하였다. 소결된 시편은 경면 연마하여 주사전자현미경으로 미세 조직을 관찰하였다. TiCN-30Co 조성 시편은 corner-round 모양의 입자 모양으로 소결 시간 증가에 따라 빠른 입자 성장을 나타내었다 .(7STiCN+2SWC)-30Co 조성 시변의 경우 일반적으로 보고된 바와 같이 core/shell 구조를 나타내었으며, core는 TiC-rich 상이었고, shell은 (Ti,W)(C,N) 복합 탄화물 상이었다. WC 함량이 중가함에 따라 입자의 corner-round 영역이 증가하였으며 (SOTiCN-SOWC)-30Co 조성 근처에서는 거의 둥근 형태의 입자 모양을 나타내었다. 또한 TiCN - 30Co 조성 시편에 비하여 WC가 첨가된 시펀들은 작은 평균입자크기를 나타내었다. 본 연구의 결과는 shell 영역 조성 변화는 계면에너지 이방성과 기지상 내의 펑형 입자 모양을 변화시키고 나아가 입자 성장 속도 에도 영향을 미친다는 것을 보여준다.

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Evaluation of Characteristics of Anisotropic Deformation in Manufacturing of Large-scale Glass-ceramic Composite Sintered Body (대형 유리-세라믹 복합 매질 소결체 제조 시 비등방성 변형 특성 평가)

  • Kim, Kwang-Wook;Sohn, Sungjune;Kim, Jimin;Foster, Richard I.;Lee, Keunyoung
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.18 no.1
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    • pp.31-41
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    • 2020
  • We studied the anisotropic shrinkage and deformation characteristics of large size sintered bodies in the manufacturing of glass-ceramic composite wasteform. We used uranium-bearing waste, generated from the treatment of spent uranium catalyst. Sintered specimens were prepared in several forms, comprising a circular disk, and a quarter disk in several diameters of up to 40 cm. Regardless of form or size, the sintered bodies had high isotropic shrinkage when they were fabricated using green bodies prepared at 60 MPa. The average anisotropy rate and average shrinkage rate were 1.6%, and 37.4%, respectively. We confirmed that the glass-ceramic composite wasteform in a large scale disk-type for packing in a 200 L drum could be fabricated with a tolerable anisotropy shrinkage. This has resulted in a significant reduction in the volume of radioactive waste to be disposed of with highly stable wasteform.

A Study of EPMA Analysis for Nitric Acid Insoluble Alloys (질산불용성 합금의 EPMA분석)

  • Park, Soon-Dal;Park, Yong-Joon;Kim, Jong-Goo;Son, Se-Chul;Joe, Kih-Soo
    • Analytical Science and Technology
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    • v.11 no.6
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    • pp.485-494
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    • 1998
  • Ternary and quaternary alloys composed of Mo-Ru-Rh-Pd were prepared and their crystal structure and quantitative chemical compositions were analysed by XRD, WDX, EDX and ICP/AES. The results of X-ray diffraction studies showed that the alloys were crystallized in hexagonal close packing, well known as ${\varepsilon}$-phase with $P6_3/mmc$ of space group. The optimum accelerating voltage for Zr~Cd(40~48) analyzed by EPMA using PET crystal was found to be 15 kV and the linear regression coefficient(R) of atomic number and X-ray intensity was approximately 0.998 without Tc standard specimen. The WDX results of alloys of Mo and Pd by linear regression equations were detected to be 0.1% lower compared to WDX analysis results using standard specimen, while Ru, Rh were detected 3% higher. These alloys were completely dissolved in mixed acid of 12.5 mL HCl and 1 mL $HNO_3$, at $220^{\circ}C$ for 22 hours using autoclave with PTFE vessel. There was no reprecipitating phenomnon when diluted 100 times with 1N-HCl. The results of ICP/AES analysis deviated less than 4% comparing with those of normal WDX analysis.

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Changes of Fruit Quality in Response to Storage on Sweet Pepper (Capsicum annuum L.) Cultivars in Summer (여름 착색단고추의 저장에 따른 품종별 품질 변화)

  • An Chul-Geon;Hwang Hae-Jun;Shim Jae-Suk;Chong Byeong-Mahn;Shon Gil-Man;Song Geun-Woo;Lim Chae-Shin;Cho Jeoung-Lai
    • Journal of Bio-Environment Control
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    • v.15 no.2
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    • pp.177-183
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    • 2006
  • The summer production of sweet pepper in Korea which cultured in the highland area such as Hapchon is essential for a year-round export, but has the problem, fruits lose easily those marketability. This study was carried out to find changes of fruit quality in response to storage on sweet pepper cultivars in summer. Seven cultivars of sweet peppers, 'Jubilee', 'Plenty', 'Goal', 'Romeca', 'Derby', 'Midas' and 'Maximalia' were obtained iron growers in Hapchon which was highland of 600-800m from sea level and stored at $10^{\circ}C$ with box packing. Fruit quality was evaluated every 4days up to 4weeks. The weight loss of 'Jubilee' was the lowest, that of 'Romeca' was the highest. The firmness of 'Goal' was maintained highly for 4weeks and the red cultivars was higher than those of other color cultivars. The lightness of 'Jubilee' was sensitively affected by storage duration. Seeds of 'Plenty' and 'Derby' were plentifully browned after 4weeks storage. The occurrence of fruit rotting was after 16-204ay storage and those of 'Plenty' and 'Maximalia' were the earliest. The marketability of 'Jubilee' and 'Romeca' maintained by 70% for 16 days was the highest, but most cultivars lost those by 20% after 24days storage. It may be suggested that the marketability of sweet pepper producted in summer can be stored at $10^{\circ}C$ for 2weeks to maintain that of 80%.

Development of Epoxy/Boron Nitride Composites for High Heat Dissipation of Metal Copper Clad Laminate (MCCL) (Metal Copper Clad Laminate (MCCL)의 고방열 특성을 위한 Epoxy/BN 복합체 개발)

  • Choi, Ho-Kyoung;Choi, Jae-Hyun;Choi, Bong-Goo;Yoon, Do-Young;Choi, Joong-So
    • Korean Chemical Engineering Research
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    • v.58 no.1
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    • pp.64-68
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    • 2020
  • In this study, metal copper clad laminate can be prepared using epoxy composite filled with thermally conductive fillers. In order to improve the thermal conductivity of epoxy composites, it is important factor to form conductive networks through appropriate packing of conductive fillers in epoxy composite matrix and to decrease the amount of thermally resistant junctions involving a epoxy composite matrix layer between adjacent filler units. This is because epoxy has a thermal conductivity of only 0.2-0.3W, so in order to maintain high thermal conductivity, thermally conductive fillers are connected to each other, so that the gap between particles can be reduced to reduce thermal resistance. The purpose of this study is to find way to achieve highly thermally conductive in the epoxy composite matrix filled with Al2O3 and Boron Nitride(BN) filler by filler loading and uniform dispersion. As a results, the use of Al2O3/BN hybrid filler in epoxy matrix was found to be effective in increasing thermal conductivity of epoxy composite matrix due to the enhanced connectivity offered by more continuous thermally conductive pathways and uniform dispersion without interfacial voids in epoxy composite matrix. In addition, surface treatmented s-BN improves the filler dispersion and adhesion between the filler and the epoxy matrix, which can significantly decrease the interfacial thermal resistance and increase the thermal conductivity of epoxy composite matrix.