• Journal of Radiation Industry
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• v.17 no.2
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• pp.127-134
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• 2023

Pharmacokinetic (PK) data provide pivotal information in drug development, and they are usually first studied in the preclinical stage using various animals. However, quite often, animal PK data may not match with human PK, especially in metabolites. Thus, most regulatory agencies in the world make it mandatory to obtain metabolite information using ¹⁴C radiolabeled drug in human for small molecule drug candidates. However, such studies are expensive and time consuming and they are usually done at the end of Phase II trials using ~3.7 MBq of ¹⁴C labeled drug in a limited number of human subjects. Introduction of accelerator mass spectrometry (AMS) in this kind of study has revolutionized it. Since AMS can measure ¹⁴C level as close as natural abundance, it can quantify the amounts of ¹⁴C labeled drugs and their metabolites produced in human body that consumes less than the amount of 0.0037 MBq of ¹⁴C labeled drug, a very safe level of radioactive dose in human. Therefore, it is now possible to conduct human ¹⁴C studies safely in early clinical trials without spending hefty amount of money and time. Korea Radioisotope Center for Pharmaceuticals(KRICP) at Korea Institute of Biological and Medical Sciences(KIRAMS) has established an AMS facility in 2018, housing a 0.5MV AMS manufactured at the US National Electrostatics Corps (NEC). The AMS instrument has been validated using various standard samples that have been prepared at Lawrence Livermore National Laboratory in the US, a worldly reputable provider of AMS standards. In this paper, we present a mass balance study for acetaminophen in rats using AMS and prove that the study results are equivalent with those of literature, which shows the AMS facilities at KRICP has successfully installed and be ready to be used in the various PK studies using ¹⁴C labelled compounds for new drug development.

• Analytical Science and Technology
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• v.7 no.2
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• pp.213-224
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• 1994

Several isotopomers of cyclooctanone were prepared by selective deuterium substitution. Intrinsic isotope effects on $^{13}C$ NMR chemical shifts of these isotopomers were investigated systematically at low temperature. These istope effects were discussed in relation to the preferred boat-chair conformation of cyclooctanone. Deuterium isotope effects on NMR chemical shifts have been known for a long time. Especially in a conformationally mobile molecule, isotope perturbation could affect NMR signals through a combination of isotope effects on equilibria and intrinsic effects. The distinction between intrinsic and nonintrinsic effects is quite difficult at ambient temperature due to involvement of both equilibrium and intrinsic isotope effects. However if equilibria between possible conformers of cyclooctanone are slowed down enough on the NMR time scale by lowering temperature, it should be possible to measure intrinsic isotope shifts from the separated signals at low temperature. $^{13}C$ NMR has been successfully utilized in the study on molecular conformation in solution when one deals with stable conformers or molecules were rapid interconversion occurs at ambient temperature. The study of dynamic processes in general requires analysis of spectra at several temperature. Anet et al. did $^1H$ NMR study of cyclooctanone at low temperature to freeze out a stable conformation, but were not able initially to deduce which conformation was stable because of the complexity of alkyl region in the $^1H$ NMR spectrum. They also reported the $^1H$ and $^{13}C$ NMR spectra of the $C_9-C_{16}$ cycloalkanones with changing temperature from $-80^{\circ}C$ to $-170^{\circ}C$, but they did not report a variable temperature $^{13}C$ NMR study of cyclooctanone. For the analysis of the intrinsic isotope effect with relation to cylooctanone conformation, $^{13}C$ NMR spectra are obtained in the present work at low temperatures (up to $-150^{\circ}C$) in order to find the chemical shifts at the temperature at which the dynamic process can be "frozen-out" on the NMR time scale and cyclooctanone can be observed as a stable conformation. Both the ring inversion and pseudorotational processes must be "frozen-out" in order to see separate resonances for all eight carbons in cyclooctanone. In contrast to $^1H$ spectra, slowing down just the ring inversion process has no apparent effects on the $^{13}C$ spectra because exchange of environments within the pairs of methylene carbons can still occur by the pseudorotational process. Several isotopomers of cyclooctanone were prepared by selective deuterium substitution (fig. 1) : complete deuterium labeling at C-2 and C-8 positions gave cyclooctanone-2, 2, 8, $8-D_4$ : complete labeling at C-2 and C-7 positions afforded the 2, 2, 7, $7-D_4$ isotopomer : di-deuteration at C-3 gave the 3, $3-D_2$ isotopomer : mono-deuteration provided cyclooctanone-2-D, 4-D and 5-D isotopomers : and partial deuteration on the C-2 and C-8 position, with a chiral and difunctional case catalyst, gave the trans-2, $8-D_2$ isotopomer. These isotopomer were investigated systematically in relation with cyclooctanone conformation and intrinsic isotope effects on $^{13}C$ NMR chemical shifts at low temperature. The determination of the intrinsic effects could help in the analysis of the more complex effects at higher temperature. For quantitative analysis of intrinsic isotope effects, the $^{13}C$ NMR spectrum has been obtained for a mixture of the labeled and unlabeled compounds because the signal separations are very small.

• 대한핵의학회:학술대회논문집
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• 1969.12a
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• pp.1.2-1.2
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• 1969

• Bulletin of the Korean Space Science Society
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• 1998.10a
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• pp.52.1-52
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• 1998

No Abstract.See Full-text

• 대한핵의학회:학술대회논문집
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• 1970.10a
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• pp.87.2-88
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• 1970

• Proceedings of the KSEEG Conference
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• 2002.04a
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• pp.59-61
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• 2002

• Journal of the Korean Chemical Society
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• v.67 no.2
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• pp.116-119
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• 2023

• Journal of Conservation Science
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• v.30 no.4
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• pp.345-351
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• 2014

Chemical and Pb isotope analysis were performed in order to determine the origin of bronze artefacts excavated from the Inyongsaji site in South Korea. The result of ICP-MS shows that they are tin bronzes in which lead was not intentionally added during production. Pb isotope data analyzed by TIMS are plotted in the southern region of Korea and China of the distribution map drawn by Mabuchi(1985). On the other hand, the identical isotope data are plotted in the Taebaek basin and the Olcheon metamorphic belt correspondent to zone2 and zone3 respectively. It is believed that the isotope data on the tin bronzes which have very low lead content can be used to trace the origin of copper ore rather than those of either lead or tin ore. Pb istope analysis allows diverse interpretation as it can be applied to any object containing trace amounts of lead. In addition, accumulation of isotope data as well as further studies will improve reliability of the provenance studies.

• Korean Journal of Ecology and Environment
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• v.50 no.4
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• pp.432-440
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• 2017

Compound specific isotope analysis of amino acids (CSIA-AAs) is being highlighted as an alternative approach for overcoming some restrictions in application of stable isotope analysis of bulk tissue (SIA) for trophic position (TP) estimation. However, this approach has rarely been applied in Korea. The present study determines TP of two Polychaeta (Nephtyidae and Glyceridae) and two fish species(Platycephalus indicus and Lophius litulon) collected from the Geum River estuary using nitrogen isotope ratio of amino acid and compared with the TP values estimated by SIA. The Polychaeta species, sampled in two sites, showed similar TP between SIA(2.7 and 3.1) and CSIA-AAs (2.6 and 3.1). However, for both fish species, TP values displayed a large difference between SIA (3.1 and 2.3) and CSIA-AAs (3.8 and 3.7). In this study TP values estimated by CSIA-AAs showed more similar to the previously reported gut content analysis of both fishes compared with the results of SIA. Current study suggests the applicability of nitrogen isotope ratio of amino acid to understand coastal ecosystem structure and trophic ecology.

• Analytical Science and Technology
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• v.16 no.6
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• pp.450-457
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• 2003

The determination of uranium and its isotopes in spent nuclear fuels by isotope dilution mass spectrometry (IDMS) has been studied. The spent fuel samples were dissolved in 8 M $HNO_3$ or its mixture with 14 M $HNO_3-0.05M$ HF. The dissolved solutions were filterred on membrane filter with $1.2{\mu}m$ pore size. The uraniums in the spiked and unspiked sample solutions were quantitatively adsorbed by anion exchange resin, AG 1X8 and eluted with 0.1 M HCl. The contents of uranium and its isotopes ($^{234}U$, $^{235}U$, $^{236}U$ 및 $^{238}U$) in the spent fuel samples were determined by isotope dilution mass spectrometric method using $^{233}U$ as spike. The spike reference solution was standarized by reverse isotope dilution mass spectrometry (R-IDMS) using natural and depleted uranium. The results from IDMS were in average relative difference of 0.34% when compared with those by the potentiometric titration method.