• Title/Summary/Keyword: Phase transitions

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Rapid and Simple Method for the Determination of Pregabalin in Human Plasma using Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS): Application to a Bioequivalence Study of Daewoong Pregabalin Capsule To Lyrica® Capsule (Pregabalin 150 mg)

  • Jang, Ki-Ho;Seo, Ji-Hyung;Yim, Sung-Vin;Lee, Kyung-Tae
    • Journal of Pharmaceutical Investigation
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    • v.41 no.4
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    • pp.255-262
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    • 2011
  • Method using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of pregabalin in plasma samples. Acquisition was performed by monitoring the transitions: m/z 160.1${\rightarrow}$142.2 for pregabalin and m/z 423.2${\rightarrow}$207.1 for losartan (as an internal standard). After cold acetonitrileinduced protein precipitation of the plasma samples, separation was performed with C18 column by isocratic mobile phase consisted of 10 mM ammonium acetate and acetonitrile (15:85, v/v). Results were linear over the concentration ranged from 0.1 to $10{\mu}g$/mL and the correlation coefficients (r) were $\geq0.99$. Intra- and inter-day precisions were $\leq6.02$ and $\leq11.04%$, respectively, and intra- and inter-day accuracies were 96.60-101.09 and 98.10-102.60%, respectively. This validated method was successfully applied to a bioequivalence study of two formulations of pregabalin, Daewoong pregabalin capsule (Daewoong Pharm. Co., Ltd.) and Lyrica$^{(R)}$ capsule (Pfizer Korea Ltd.) in twenty eight healthy Korean volunteers. The subjects received a single oral dose of each formulation (150 mg as pregabalin) in a randomized $2{\times}2$ crossover study and plasma samples were obtained from each subject at predetermined time intervals. Then, the pharmacokinetic parameters ($AUC_{0-t}$, $C_{max}$ and $T_{max}$) were calculated and statistically analyzed to assess the differences between two formulations. The 90% confidence intervals for the log-transformed data were acceptable range of log 0.8-log 1.25 (e.g., log 1.0048-log 1.0692 for AUC0-t, log 0.9142-log 1.0421 for $C_{max}$). Thus, $AUC_{0-t}$ and $C_{max}$ met the criteria of the Korea Food and Drug Administration (KFDA) for bioequivalence test indicating that Daewoong pregabalin capsule was bioequivalent to Lyrica$^{(R)}$ capsule.

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.

A Study on Anisotropic Compression Behavior of Illite (일라이트의 비등방적 압축특성 연구)

  • Yun, Seohee;Lee, Yongjae
    • Korean Journal of Mineralogy and Petrology
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    • v.33 no.1
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    • pp.11-18
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    • 2020
  • High-pressure synchrotron X-ray powder diffraction experiments were performed on natural illite (K0.65Al2(Al0.65Si3.35)O10(OH)2) using diamond anvil cell (DAC) under two different pressure transmitting media (PTM), i.e., water and ME41 (methanol:ethanol = 4:1 by volume). When using water as PTM, occasional heating was applied up to about 250℃ while reaching pressure up to 2.7 GPa in order to promote both hydrostatic conditions and intercalation of water molecules into the layer. When using ME41, pressure was reached up to 6.9 GPa at room temperature. Under these conditions, illite did not show any expansion of interlayer distance or phase transitions. Pressure-volume data were used to derive bulk moduli (K0) of 45(3) GPa under water and 51(3) GPa under ME41 PTM. indicating no difference in compressibility within the analytical error. Linear compressibilities were then calculated to be βa = 0.0025, βb = 0.0029, βc = 0.0144 under ME41 PTM showing the c-axis is ca. six times more compressible than a- and b-axes. These elastic behaviors of illite were compared to muscovite, one of its structural analogues.

Spot marking of the multilayer thin films by Nd:YAG laser (Nd:YAG 레이저에 의한 다층 박막의 미소 점 마킹)

  • Kim, Hyun-Jin;Shin, Yong-Jin
    • Korean Journal of Optics and Photonics
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    • v.15 no.4
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    • pp.361-368
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    • 2004
  • We separated the multilayer structure of CD-R(compact disk-recordable) and investigated optimal spot marking conditions and physical and chemical transitions in response to various laser beam energh levels. Spot marking(80 ${\mu}{\textrm}{m}$ spot size) was produced on the surface of each layer using a Q-switched Nd:YAG laser between 27 mJ and 373mJ. By investigating resulting pit formation with Optical Microscopy(OM) and Optical Coherence Tomography(OCT), we analyzed the formation process of spot marking in the multilayer structure of different chemical composition. The localized heating of the substrate in the multilayer thin film caused the short temporal thermal expansion, and absorbed optical energy between reflective and dye interfaces melted dye and increased the volume. During the cooling phase, formation of pit and surrounding rim can be explained by three distinct processes; effect of surface tension, evaporation by spontaneous temperature increase due to laser energy, and mass flow from the recoil pressure. Our results shows that the spot marking formation process in the multilayer thin film is closely related to the layers' physical, chemical, and optical properties, such as surface tension, melt viscosity, layer thickness, and chemical composition.

A Computational Mineralogy Study of the Crystal Structure and Stability of Aluminum Silicate (Al2SiO5) Minerals (알루미늄 규산염(Al2SiO5) 광물의 결정구조와 안정성에 대한 계산광물학 연구)

  • Kim, Juhyeok;Son, Sangbo;Kwon, Kideok D.
    • Journal of the Mineralogical Society of Korea
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    • v.31 no.1
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    • pp.13-22
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    • 2018
  • Aluminum silicates ($Al_2SiO_5$) undergo phase transitions among kyanite, andalusite, and sillimanite depending on temperature and pressure conditions. The minerals are often used as an important indicator of the degree of metamorphism for certain metamorphic rocks. In this study, we have applied classical molecular dynamics (MD) simulations and density functional theory (DFT) to the aluminum silicates. We examined the crystal structures as a function of applied pressure and the corresponding stabilities based on calculated enthalpies at each pressure. In terms of the lattice parameters, both methods showed that the volume decreases as the pressure increases as observed in the experiment. In particular, DFT results differed from experimental results by much less than 1%. As to the relative stability, however, both methods showed different levels of accuracy. In the MD simulations, a transition pressure at which the relative stability between two minerals reverse could not be determined because the enthalpies were insensitive to the applied pressure. On the other hand, in DFT calculations, the relative stability relation among the three minerals was consistent with experiment, although the transition pressure was strongly dependent on the choice of the electronic exchange-correlation functional.

Uniform Posture Map Algorithm to Generate Natural Motion Transitions in Real-time (자연스러운 실시간 동작 전이 생성을 위한 균등 자세 지도 알고리즘)

  • Lee, Bum-Ro;Chung, Chin-Hyun
    • Journal of KIISE:Computing Practices and Letters
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    • v.7 no.6
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    • pp.549-558
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    • 2001
  • It is important to reuse existing motion capture data for reduction of the animation producing cost as well as efficiency of producing process. Because its motion curve has no control point, however, it is difficult to modify the captured data interactively. The motion transition is a useful method to reuse the existing motion data. It generates a seamless intermediate motion with two short motion sequences. In this paper, Uniform Posture Map (UPM) algorithm is proposed to perform the motion transition. Since the UPM is organized through quantization of various postures with an unsupervised learning algorithm, it places the output neurons with similar posture in adjacent position. Using this property, an intermediate posture of two active postures is generated; the generating posture is used as a key-frame to make an interpolating motion. The UPM algorithm needs much less computational cost, in comparison with other motion transition algorithms. It provides a control parameter; an animator could control the motion simply by adjusting the parameter. These merits of the UPM make an animator to produce the animation interactively. The UPM algorithm prevents from generating an unreal posture in learning phase. It not only makes more realistic motion curves, but also contributes to making more natural motions. The motion transition algorithm proposed in this paper could be applied to the various fields such as real time 3D games, virtual reality applications, web 3D applications, and etc.

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Synthesis and Defect-Structure Analysis of $ThO_2-Tm_2O_3$ Solid Solutions ($ThO_2-Tm_2O_3$ 고용체의 합성 및 결함구조해석)

  • Don Kim;Chang Kwon Kang;Keu Hong Kim;Jae Shi Choi
    • Journal of the Korean Chemical Society
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    • v.31 no.6
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    • pp.491-497
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    • 1987
  • $ThO_2-Tm_2O_3$ (TDT) solid solutions containing 1,3,5,8,10, and 15 mol% $Tm_2O_3$ were synthesized from spectroscopically pure $ThO_2$ and $Tm_2O_3$ polycrystalline powders. The TDT solid solutions were indentified to the fluorite structure by the X-ray powder technique. The values of the lattice parameter were decreased with increasing amount of $Tm_2O_3$ incorporated. But, there was no linearity for the samples containing 8, 10, and 15 mol% $Tm_2O_3$. It was concluded that these samples became incomplete solid solutions. From the intensity analyses of X-ray diffraction patterns, the residual factor was found below 0.13 even for the 15 mol% TDT system. lt was confirmed from the DTA and TGA analyses that any phase transitions did not occur under the experimental condition executed. Comparing the pycnometric density with the lattice parameter obtained from XRD, it was suggested that the predominant defect model be an oxygen vacancy.

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Sensitive determination of paroxetine in canine plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS) (LC-MS/MS를 이용한 비글견 혈장 중 파록세틴의 고감도 분석)

  • Chang, Kyu Young;Kang, Seung Woo;Han, Sang Beom;Youm, Jeong-Rok;Lee, Kyung Ryul;Lee, Hee Joo
    • Analytical Science and Technology
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    • v.20 no.2
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    • pp.138-146
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    • 2007
  • A simple and sensitive method for the determination of paroxetine in canine plasma was developed and validated by liquid-liquid extraction and liquid chromatography-tandem mass spectrometry (LC-/MS/MS). Fluoxetine was used as an internal standard. Paroxetine and internal standard in plasma samples were extracted using TBME (tert-butyl methyl ether). A centrifuged upper layer was then evaporated and reconstituted with mobile phase of 50% acetonitrile adjusted to pH 3 by formic acid. The reconstituted samples were injected into a Capcell Pak UG120 ($2.0{\times}150mm$, $5{\mu}m$) column. Using MS/MS with SRM (selective reaction monitoring) mode, the transitions (precursor to product) monitored were m/z $330{\rightarrow}192$ for paroxetine, and m/z $310{\rightarrow}148$ for internal standard. Linear detection responses were obtained for paroxetine concentration range of 0.02~5 ng/mL. A correlation coefficient of linear regression ($R^2$) was 0.9993. Detection of paroxetine in canine plasma was accurate and precise, with limit of quantification at 0.02 ng/mL. The method has been successfully applied to pharmacokinetic study of paroxetine in healthy beagle dogs.

Analysis of clenbuterol in bovine muscle and milk by LC-ESI/MS/MS (LC-ESI/MS/MS를 이용한 소고기와 우유에서의 클렌부테롤 분석)

  • Hong, Selyung;Jeong, Jiyoon;Park, Hyejin;Lee, Soonho;Lee, Jongok
    • Analytical Science and Technology
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    • v.21 no.6
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    • pp.535-542
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    • 2008
  • A liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI/MS/MS) method was developed for the determination and confirmation of clenbuterol in bovine muscle and milk. Clenbuterol and clenbuterol-D9 using as an internal standard in samples were extracted with ethyl acetate after hydrolysis and evaporated to dryness. The extracts were dissolved in 20% methanol and cleaned using HLB solid-phase extraction cartridge. The analytes were detected by LC-ESI/MS/MS on a $C_{18}$ column. Mass spectral acquisition was done in selected reaction monitoring (SRM) in positive ion mode to provide a high degree of sensitivity. Using MS/MS with SRM mode, the transitions (precursor to product) monitored were m/z 277${\rightarrow}$203 for clenbuterol, and m/z 286${\rightarrow}$204 for internal standard. The limits of quantitation (LOQ) and mean recoveries of clenbuterol in bovine muscle were $0.2{\mu}g/kg$ and 84.3~91.1%, respectively. The LOQ and mean recoveries in milk were $0.05{\mu}g/kg$ and 87.7~98.3%, respectively.

Structural Behavior of Mixed $LiMn_2O_4-LiNi_{1/3}Co_{1/3}Mn_{1/3}O_2$ Cathode in Li-ion Cells during Electrochemical Cycling

  • Yun, Won-Seop;Lee, Sang-U
    • Proceedings of the Materials Research Society of Korea Conference
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    • 2011.05a
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    • pp.5-5
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    • 2011
  • The research and development of hybrid electric vehicle (HEV), plug-in hybrid electric vehicle (PHEV) and electric vehicle (EV) are intensified due to the energy crisis and environmental concerns. In order to meet the challenging requirements of powering HEV, PHEV and EV, the current lithium battery technology needs to be significantly improved in terms of the cost, safety, power and energy density, as well as the calendar and cycle life. One new technology being developed is the utilization of composite cathode by mixing two different types of insertion compounds [e.g., spinel $LiMn_2O_4$ and layered $LiMO_2$ (M=Ni, Co, and Mn)]. Recently, some studies on mixing two different types of cathode materials to make a composite cathode have been reported, which were aimed at reducing cost and improving self-discharge. Numata et al. reported that when stored in a sealed can together with electrolyte at $80^{\circ}C$ for 10 days, the concentrations of both HF and $Mn^{2+}$ were lower in the can containing $LiMn_2O_4$ blended with $LiNi_{0.8}Co_{0.2}O_2$ than that containing $LiMn_2O_4$ only. That reports clearly showed that this blending technique can prevent the decline in capacity caused by cycling or storage at elevated temperatures. However, not much work has been reported on the charge-discharge characteristics and related structural phase transitions for these composite cathodes. In this presentation, we will report our in situ x-ray diffraction studies on this mixed composite cathode material during charge-discharge cycling. The mixed cathodes were incorporated into in situ XRD cells with a Li foil anode, a Celgard separator, and a 1M $LiPF_6$ electrolyte in a 1 : 1 EC : DMC solvent (LP 30 from EM Industries, Inc.). For in situ XRD cell, Mylar windows were used as has been described in detail elsewhere. All of these in situ XRD spectra were collected on beam line X18A at National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory using two different detectors. One is a conventional scintillation detector with data collection at 0.02 degree in two theta angle for each step. The other is a wide angle position sensitive detector (PSD). The wavelengths used were 1.1950 ${\AA}$ for the scintillation detector and 0.9999 A for the PSD. The newly installed PSD at beam line X18A of NSLS can collect XRD patterns as short as a few minutes covering $90^{\circ}$ of two theta angles simultaneously with good signal to noise ratio. It significantly reduced the data collection time for each scan, giving us a great advantage in studying the phase transition in real time. The two theta angles of all the XRD spectra presented in this paper have been recalculated and converted to corresponding angles for ${\lambda}=1.54\;{\AA}$, which is the wavelength of conventional x-ray tube source with Cu-$k{\alpha}$ radiation, for easy comparison with data in other literatures. The structural changes of the composite cathode made by mixing spinel $LiMn_2O_4$ and layered $Li-Ni_{1/3}Co_{1/3}Mn_{1/3}O_2$ in 1 : 1 wt% in both Li-half and Li-ion cells during charge/discharge are studied by in situ XRD. During the first charge up to ~5.2 V vs. $Li/Li^+$, the in situ XRD spectra for the composite cathode in the Li-half cell track the structural changes of each component. At the early stage of charge, the lithium extraction takes place in the $LiNi_{1/3}Co_{1/3}Mn_{1/3}O_2$ component only. When the cell voltage reaches at ~4.0 V vs. $Li/Li^+$, lithium extraction from the spinel $LiMn_2O_4$ component starts and becomes the major contributor for the cell capacity due to the higher rate capability of $LiMn_2O_4$. When the voltage passed 4.3 V, the major structural changes are from the $LiNi_{1/3}Co_{1/3}Mn_{1/3}O_2$ component, while the $LiMn_2O_4$ component is almost unchanged. In the Li-ion cell using a MCMB anode and a composite cathode cycled between 2.5 V and 4.2 V, the structural changes are dominated by the spinel $LiMn_2O_4$ component, with much less changes in the layered $LiNi_{1/3}Co_{1/3}Mn_{1/3}O_2$ component, comparing with the Li-half cell results. These results give us valuable information about the structural changes relating to the contributions of each individual component to the cell capacity at certain charge/discharge state, which are helpful in designing and optimizing the composite cathode using spinel- and layered-type materials for Li-ion battery research. More detailed discussion will be presented at the meeting.

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