Development of a sensitive liquid chromatography-electrospray ionization mass spectrometry method for the measurement of KW-5139 in rat plasma |
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Authors: | Yamaguchi K Takashima M Uchimura T Kobayashi S |
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Institution: | Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co. Ltd, 1188 Shimotogari Nagaizumi-cho, Shizuoka-ken 411, Japan. |
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Abstract: | A sensitive method for the determination of a prokinetic peptide, KW-5139 (Leu(13)-motilin), in rat plasma has been developed utilizing liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). KW-5139 was separated by reversed-phase HPLC, with a mixture of 75 mM ammonium formate (pH 3.0) and acetonitrile (4:1, v/v), and monitored by single ion recording (SIR)-ESI-MS at m/z 894 (M+3H](3+)). Simple protein precipitation and the LC-ESI-MS analysis allowed the determination of KW-5139 in rat plasma with the mean precision and accuracy at the lower limit of quantitation (LLOQ, 0.5 ng/mL) of 5.7 and 11.2%, respectively. The method was applied to the monitoring of the plasma time-concentration profile of KW-5139, intravenously administered to rats at a dose of 1 microg/kg. |
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