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Validation of LC-MS/MS Method for Determination of Rabeprazole in Human Plasma : Application of Pharmacokinetics Study (인체 혈장중 라베프라졸의 정량을 위한 LC-MS/MS 분석법 검증 및 단일 용량 투여에 의한 약물동태 연구)

  • Tak, Sung-Kwon;Seo, Ji-Hyung;Ryu, Ju-Hee;Choi, Sang-Joon;Lee, Myung-Jae;Kang, Jong-Min;Lee, Jin-Sung;Hong, Seung-Jae;Yim, Sung-Vin;Lee, Kyung-Tae
    • Journal of Pharmaceutical Investigation
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    • v.39 no.1
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    • pp.73-78
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    • 2009
  • A simple LC-MS/MS method of rabeprazole in human plasma was developed and validated. Rabeprazole and Internal standard (I.S), omeprazole, were extracted from human plasma by liquid liquid extraction, chromatographic separation of rabaprazole in plasma was achieved at $45^{\circ}C$ with a Shiseido UG120 $C_{18}$ column and methanol-10 mM ammonium acetate buffer (pH 9.42 with ammonium water), as mobile phase. Rabeprazole produced a protonated precursor ion [$(M+H)^+$] at m/z 360.10 and corresponding product ion at m/z 242.21. Internal standard produced a protonated precursor ion [$(M+H)^+$] at 346.09 and corresponding product ion at m/z 198.09. This method showed linear response over the concentration range of $1{\sim}500\;ng/mL$ with correalation coefficient greater than 0.99. The lower limit of quantitation (LLOQ) using 0.2 mL plasma was 1 ng/mL, which was sensitive enough for pharmacokinetics studies. The method was specific and validated with a limit of quantitation of 1 ng/mL. The intra-day and inter-day precision and accuracy were acceptable for all samples including the LLOQ. The applicability of the method was demonstrated by analysis of plasma after administration of a single 10 mg dose to 36 healthy subject. From the plasma rabeprazole concentration versus time curves, the mean $AUC_t$ (The area under the plasma concentration-time curve from time 0 to 12 hr ) was $691.36{\pm}321.88\;ng{\cdot}hr/mL$, $C_{max}$ (maximum plasma drug concentration) of $353.21{\pm}131.52\;ng/mL$ reached $3.4{\pm}1.1\;hr$ after adiministration. The mean biological half-life of rabeprazole was $1.37{\pm}0.75\;hr$. Based on the results, this simple method could readily be used in pharmacokinetics studies.

A Study on the Automation Algorithm to Identify the Geological Lineament using Spatial Statistical Analysis (공간통계분석을 이용한 지질구조선 자동화 알고리즘 연구)

  • Kwon, O-Il;Kim, Woo-Seok;Kim, Jin-Hwan;Kim, Gyo-Won
    • The Journal of Engineering Geology
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    • v.27 no.4
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    • pp.367-376
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    • 2017
  • Recently, tunneling under the seabed is becoming increasingly common in many countries. In Korea, there are proposals to tunnel from the mainland to Jeju Island. Safe construction requires geologic structures such as faults to be characterized during the design and construction phase; however, unlike on land, such structures are difficult to survey seabed. This study aims to develop an algorithm that uses geostatistics to automatically derive large-scale geological structures on the seabed. The most important considerations in this method are the optimal size of the moving window, the optimal type of spatial statistics, and determination of the optimal percentile standard. Finally, the optimal analysis algorithm was developed using the R program, which comprehensibly presents variations in spatial statistics. The program allows the type and percentile standard of spatial statistics to be specified by the user, thus enabling an analysis of the geological structure according to variations in spatial statistics. The geotechnical defense-training algorithm shows that a large, linear geological lineament is best visualized using a $3{\times}3$ moving window and a 10% upper standard based on the moving variance value and fractile. In particular, setting the fractile criterion to the upper 0.5% almost entirely eliminates the error values from the contour image.

Effects of Dissolved Oxygen Level on Avermectin $B_{1a}$ Production by Streptomyces avermitilis in Computer-Controlled Bioreactor Cultures

  • Song, Sung-Ki;Jeong, Yong-Seob;Kim, Pyeung-Hyeun;Chun, Gie-Taek
    • Journal of Microbiology and Biotechnology
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    • v.16 no.11
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    • pp.1690-1698
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    • 2006
  • In order to investigate the effect of dissolved oxygen (DO) level on AVM $B_{1a}$ production by a high yielding mutant of Streptomyces avermitilis, five sets of bioreactor cultures were performed under variously controlled DO levels. Using an online computer control system, the agitation speed and aeration rate were automatically controlled in an adaptive manner, responding timely to the oxygen requirement of the producer microorganism. In the two cultures of DO limitation, the onset of AVM $B_{1a}$ biosynthesis was observed to casually coincide with the fermentation time when oxygen-limited conditions were overcome by the producing microorganism. In contrast, this phenomenon did not occur in the parallel fermentations with DO levels controlled at around 30% and 40% throughout the entire fermentation period, showing an almost growth-associated mode of AVM $B_{1a}$ production: AVM $B_{1a}$ biosynthesis under the environments of high DO levels started much earlier than the corresponding oxygen-limited cultures, leading to a significant enhancement of AVM $B_{1a}$ production during the exponential stage. Consequently, approximately 6-fold and 9-fold increases in the final AVM $B_{1a}$ production were obtained in 30% and 40% DO-controlled fermentations, respectively, especially when compared with the culture of severe DO limitation (the culture with 0% DO level during the exponential phase). The production yield ($Y_{p/x}$), volumetric production rate (Qp), and specific production rate (${\bar{q}}_p$) of the 40% DO-controlled culture were observed to be 14%, 15%, and 15% higher, respectively, than those of the parallel cultures that were performed under an excessive agitation speed (350 rpm) and aeration rate (1 vvm) to maintain sufficiently high DO levels throughout the entire fermentation period. These results suggest that high shear damage of the high-yielding strain due to an excessive agitation speed is the primary reason for the reduction of the AVM $B_{1a}$ biosynthetic capability of the producer. As for the cell growth, exponential growth patterns during the initial 3 days were observed in the fermentations of sufficient DO levels, whereas almost linear patterns of cell growth were observed in the other two cultures of DO limitation during the identical period, resulting in apparently lower amounts of DCW. These results led us to conclude that maintenance of optimum DO levels, but not too high to cause potential shear damage on the producer, was crucial not only for the cell growth, but also for the enhanced production of AVM $B_{1a}$ by the filamentous mycelial cells of Streptomyces avermitilis.

Retention Behaviors of Natural Gas Components on a Single Column by Gas Chromatography (기체 크로마토그래피에 의한 단일 컬럼상에서 천연가스 성분의 머무름 거동)

  • Choi, Yong-Wook;Choe, Kun-Hyung;Lee, Dai-Woon
    • Analytical Science and Technology
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    • v.7 no.3
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    • pp.329-338
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    • 1994
  • The retention behaviors of natural gas components were studied on a single column by gas chromatography. The dead time, $t_0$ was obtained by using extrapolation of homologous series to determine capacity factors. The plots of retention data for homologous series and carbon number at different temperatures were shown to converge into a single point, which point was determined as a dead time. The results of the effect of temperature on the column efficiency for n-butane exhibited the plate number, N incerased with temperature, but the resolution among the fast eluted components decreased. The adsorption enthalpy (${\Delta}H^0{_{ads}}$) for each component on 28% DC 200 stationary phase was determined, and in order to investigate the retention behaviors of natural gas components the regression analysis of log $t_R$, log k' and log ${\alpha}$ vs. van der Waals volume(Vw), molecular connectivity index(X) and hydrophobic fragmental constant(f) were carred out. Good correlation was found between log k' vs. Vw, and log k' vs. f. The correlations between the physical properties of natural gas and the physical parameters were investigated by the linear regression analysis. The relationships between Vw vs. molecular weight and heating value(${\Delta}H_{comb}$), X vs. boiling point, and f vs. molecular weight, boiling point and heating value exhibited the high correlation coefficient more than 0.99. Using the regression equation between the heating value of natural gas and Vw the predicted heating values from $C_6$ to $C_{10}$ showed good agreement with those reported in the literature within 0.2% relative error.

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Validation of LC-MS/MS method for determination of ginsenoside Rg1 in human plasma (인체 혈장 중 Ginsenoside Rg1의 정량을 위한 LC-MS/MS 분석법 검증)

  • Kim, Yunjeong;Han, Song-Hee;Jeon, Ji-Young;Hwang, Min-Ho;Im, Yong-Jin;Lee, Sun Young;Chae, Soo-Wan;Kim, Min-Gul
    • Analytical Science and Technology
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    • v.26 no.4
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    • pp.221-227
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    • 2013
  • A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the investigation of the ginsenoside Rg1 in human plasma. After addition of internal standard (digoxin), plasma was diluted with acetone and methanol (80:20), the supernatant was concentrated and analyzed by LC-MS/MS. The optimal chromatographic separation was achieved on an Agilent Eclipse XDB-C18 column ($4.6{\times}150mm$, $5{\mu}m$) with a mobile phase of 0.1% formic acid in water and 0.1% formic acid in methanol at a flow rate of 0.9 mL/min gradient mode. The standard calibration curve for ginsenoside Rg1 was linear ($r^2=0.9995$) over the concentration range 1~500 ng/mL in human plasma. The intra- and inter-day precision over the concentration range of ginsenoside Rg1 was lower than 7.53% (correlation of variance, CV), and accuracy exceeded 98.28%. This LC-MS/MS assay of ginsenoside Rg1 in human plasma is applicable for quantifying in the pharmacokinetic study.

Effects of Expander Conditioning of Complex Nursery Diets on Growth Performance of Weanling Pigs

  • Johnston, S.L.;Hines, R.H.;Hancock, J.D.;Behnke, K.C.;Traylor, S.L.;Chae, B.J.;Han, In K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.12 no.3
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    • pp.395-399
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    • 1999
  • Three experiments were conducted to determine the effects of conditioning a complex (20% whey, 10% lactose, 4% plasma protein, 4% wheat gluten and 2% blood meal) diet on growth performance of weanling pigs. In Exp. 1,180 pigs (average initial BW of 6.4 kg) were fed the experimental diet (1.7% lysine) during a 7-d growth assay. Treatments were a meal control (M), standard (ST), and expander (EX) conditioned mash or pellets. Rate and efficiency of gain were decreased by 39% and 21% (p<0.005) respectively, for pigs fed EX diets compared to those fed the ST diet. In Exp. 2,196 pigs (average initial BW of 6.5 kg) were used to determine the effects of EX operating conditions on nutritional value of a pelleted complex diet. When steam conditioning temperature (prior to expanding) was $54^{\circ}C$, increasing cone pressure of the EX from 0 to 7 to 14 kg/cm2 resulted in linear decreases in rate of gain of weaned pigs (p<0.006), suggesting heat damage of the diet. Increasing conditioning temperature (i.e., adding steam) of the diets from 46 to 54 to $63^{\circ}C$ (cone pressure at $12kg/cm^2$) resulted in improved rate of gain (p<0.04) of the pigs. However, none of the pigs fed expanded diets compared favorably to the pigs fed the conditioned $(54^{\circ}C)$ pellets processed with no cone pressure. In Exp. 3,168 pigs (average initial BW of 6.6 kg) were used to determine the effects of expanding the various components of the diet. Treatments were M and ST pellets as controls, EX-corn, EX-corn soybean-meal, EX corn-soybean meal-oil, and EX-complete diet. Efficiency of gain was increased by 13% with EX portions of the diet compared to the mash control, but there was a marked decrease in performance when the complete diet was expanded (p<0.001). Expanded corn-soybean meal-oil supported the greatest ADG with a 19% increase compared to the average of the EX corn and EX corn-soybean meal treatments (p<0.005). In conclusion, our results suggest no benefit from expanding complete phase-I diets.

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.

Effects of Local Anesthetics on the Fluidity of Synaptosomal Plasma Membrane Vesicles Isolated from Bovine Brain (국소마취제가 Synaptosomal Plasma Membrane Vesicles의 유동성에 미치는 영향)

  • Yun, Il;Han, Suk-Kyu;Baik, Seung-Wan;Kim, Nam-Hong;Kang, Jung-Sook;Chung, Joong-Ki;Lee, Eun-Joo
    • The Korean Journal of Pharmacology
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    • v.24 no.1
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    • pp.43-52
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    • 1988
  • To elucidate the mechanism of action of local anesthetics, the effects of local anethetics on the microenvironment of the lipid bilayers of synaptosomal plasma membrane vesicles (SPMV) isolated from bovine brain and dimyristoylphosphatidylcholine (DMPC) multilamellar liposomes were investigated employing the intermolecular excimer fluorescence technique and differential scanning calorimetry (DSC). The relative intensities of excimer and monomer fluorescence of pyrene are a simple linear function of the viscosity of a homologous series of solvents. The microviscosity(${\eta}$)of the hydrocarbon region of SPMV was measured by this method and the value was $57.3{\pm}5.3\;cP$ at $37^{\circ}C$. In the presence of lidocaine-HCl and procaine-HCl, the values decreased to $46.5{\pm}5.1\;cP$ and $54.7{\pm}4.8\;cP$, respectvely. The differential scanning thermograms of DMPC multilamellar liposomes showed that local anesthetics significantly lowered the phase transition temperature, broadened the thermogram peaks, and reduced the size of the cooperative unit. These results indicate that local anesthetics have significant fluidizing effects on biomembranes and perturbation of membrane lipids may produce some, but not all, of their pharmacological actions.

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Development and validation of an LC-MS/MS method for determination of compound K in human plasma and clinical application

  • Kim, Jung Soo;Kim, Yunjeong;Han, Song-Hee;Jeon, Ji-Young;Hwang, Minho;Im, Yong-Jin;Kim, Jung Hyun;Lee, Sun Young;Chae, Soo-Wan;Kim, Min-Gul
    • Journal of Ginseng Research
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    • v.37 no.1
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    • pp.135-141
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    • 2013
  • A rapid, sensitive and selective analytical method was developed and validated for the determination of compound K, a major intestinal bacterial metabolite of ginsenosides in human plasma. Liquid-liquid extraction was used for sample preparation and analysis, followed by liquid chromatography tandem spectrometric analysis and an electrospray-ionization interface. Compound K was analyzed on a Phenomenex Luna C18 column ($100{\times}2.00$ mm, 3 ${\mu}m$) with the mobile phase run isocratically with 10 mM ammonium acetate-methanol-acetonitrile (5:47.5:47.5, v/v/v) at a flow rate of 0.5 mL/min. The method was validated for accuracy (relative error <12.63%), precision (coefficient of variation <9.14%), linearity, and recovery. The assay was linear over the entire range of calibration standards i.e., a concentration range of 1 ng/mL to 1,000 ng/mL ($r^2$ >0.9968). The recoveries of compound K after liquid-liquid extraction at 1, 2, 400, and 800 ng/mL were $106.00{\pm}0.08%$, $103.50{\pm}0.19%$, $111.45{\pm}5.21%$, and $89.62{\pm}34.46%$ for intra-day and $85.40{\pm}0.08%$, $94.50{\pm}0.09%$, $112.50{\pm}5.21%$, and $95.87{\pm}34.46%$ for inter-day, respectively. The lower limit of quantification of the analytical method of compound K was 1 ng/mL in human plasma. The developed method was successfully applied to a pharmacokinetic study of compound K after oral administration in ten of healthy human subjects.

VARIABLE STARS IN THE REGION OF THE OPEN CLUSTER NGC 1039 (M34) (산개성단 NGC 1039(M34) 영역의 변광성)

  • JEON, YOUNG-BEOM;PARK, YOON-HO;LEE, SANG-MIN;LEE, UIRYEOL;KIM, DONGHYEON;JANG, HYEEUN;CHO, SUNGYOON
    • Publications of The Korean Astronomical Society
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    • v.30 no.3
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    • pp.821-832
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    • 2015
  • As a part of the short-period variability survey (SPVS) at Bohyunsan Optical Astronomy Observatory, we obtained time-series BV CCD images in the region of the open cluster NGC 1039 (M34). The observations were performed for 22 nights from July 29, 2008 to September 26, 2010. We also made LOAO observations for 10 days from September 18, 2009 to October 30, 2010 to confirm the small variabilties of ${\delta}$ Scuti-type variable stars. In this paper we presented the observational properties of 28 variable stars found in the region. They are seven ${\delta}$ Scuti-type variable stars, two ${\gamma}$ Doradus-type variable stars, four-teen eclipsing binary stars and five semi-long periodic or slow irregular variables, respectively. Only three variables were listed in the GCVS and the rest are newly discovered ones. We have performed multiple-frequency analysis to determine pulsation frequencies of the ${\delta}$ Scuti-type and ${\gamma}$ Doradus-type variable stars, using the discrete Fourier transform and linear least-square fitting methods. We also have derived the periods and amplitudes of 12 eclipsing binaries from the phase fitting method, and presented the light curves of all variable stars.