Archives of Pharmacal Research

  • 제25권5호
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  • Pages.647-651
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  • 2002
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  • 0253-6269(pISSN)
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  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

Simultaneous Determination of the Novel Neuroprotective Agent KR-31378 and its Metabolite KR-31612 Using High Performance Liquid Chromatography with Tandem Mass Spectrometry in Human Plasma

  • Kim, John (Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Department of Clinical Research, LG Life Sciences, Ltd) ;
  • Ji, Hye-Young (Medicinal Resources Research Center and Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, Wonkwang University) ;
  • Yoo, Sung-Eun (Korea Research Institute of Chemical Technology) ;
  • Kim, Sun-Ok (AgroPharma Research Institute, Dongbu Hannong Chemical Company) ;
  • Lee, Dong-Ha (Department of Clinical Research, LG Life Sciences, Ltd.) ;
  • Lim, Hong (Department of Clinical Research, LG Life Sciences, Ltd.) ;
  • Lee, Hye-Suk (Medicinal Resources Research Center and Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, Wonkwang University)
  • 발행 : 2002.10.01
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초록

An LC/MS/MS method for the simultaneous determination of a neuroprotective agent for ischemia-reperfusion damage, KR-31378 and its N-acetyl metabolite KR-31612 in human plasma was developed. KR-31378, KR-31612 and the internal standard. KR-31543 were extracted from human plasma by liquid-liquid extraction. A reverse-phase HPLC separation was performed on Luna phenylhexyl column with the mixture of acetonitrile-5 mM ammonium formate (55:45, v/v) as mobile phase. The detection of analytes was performed using an electrospray ionization tandem mass spectrometry in the multiple reaction monitoring mode. The lower limits of quantification for KR-31378 and KR-31612 were 2.0 ng/ml. The method showed a satisfactory sensitivity, precision, accuracy, recovery and selectivity.

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참고문헌

  1. Hong, K.W., Kim, K. Y., Lee, J. H., Shin, H. K., Kwak,Y. G., Kim, S. O., Lim, H. and Yoo, S. E., Neuroprotective effect of (2S,3S,4R)-N"-cyano-N-(6-amino-3,4-dihydro-3-hydroxy-2methyl-2-dimethoxymethyl-2H-benzopyran-4-yl)-N'-benzylguanidine (KR-31378), a benzopyran analog, against focal ischemic brain damage in rats. J. Pharmacol. Exp. Ther., 301, 210-216 (2002) https://doi.org/10.1124/jpet.301.1.210
  2. Kim, H. J., Kim,S. H., Kim,S.-O.,Lee, D.-H., Lim, H., Yoo, S. E. and Lee, M. G., Dose-dependent pharmacokinetics of a new neuroprotective agent for ischemia-reperfusion damage, KR31378, in rats. Biopharm. Drug Dispos., 21, 279-284 (2000) https://doi.org/10.1002/bdd.240
  3. Kim, K. Y, Kim, B. G., Kim, S. O., Yoo, S. E., Kwak, Y G.., Chae, S.W and Hong, K. W., Prevention of lipopolysaccharide-induced apoptosis by (2S,3S,4R)-N"-cyano-N-(6-amino-3,4dihydro-3-hydroxy-2-methyl-2-dimethoxymethyl-2H-benzopyran-4-yl)-N'-benzylguanidine, a benzopyran analog, in endothelial cells. J. Pharmacal. Exp. Ther., 300, 535-542 (2002) https://doi.org/10.1124/jpet.300.2.535
  4. Yoo, S. E, Yi, K. Y, Lee, S., Suh, J., Kim, N., Lee, B. H., Sea, H. W., Kim, S. O., Lee, D. H., Lim, H. and Shin, H. S., A novel anti-ischemic ATP-sensitive potassium channel opener without vasorelaxation: N-(6-aminobenzopyranyl)-N'-benzylN"-cyanoguanidine analogue. J. Med. Chem., 44, 4207-4215 (2001) https://doi.org/10.1021/jm010183f
  5. Lee, M.H., Kim, H. J., Kim, S. H., Kim, S.-O., Lee, D.-H., Lim, H., Yoo, S. E. and Lee, M. G., High-performance liquid chromatographic analysis of a new neuropratective agent far ischemia-reperfusion damage, KR-31378. Res. Com. Mol. Pathol. Pharmacol., in press.