Determination of a selective Na+/H+ exchanger inhibitor, 4-cyano(benzo[b]thiophene-2-carbonyl)guanidine (KR-33028) in rat plasma by liquid chromatography-tandem mass spectrometry |
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Authors: | Kim Young Hoon Ji Hye Young Lee Seonkyoung Yi Kyu Yang Kim You Sun Lee Kyung Hee Lee Hye Suk |
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Institution: | Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. |
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Abstract: | A liquid chromatography-tandem mass spectrometric (LC/MS/MS) method was developed for the determination of a selective Na(+)/H(+) exchanger inhibitor 4-cyano(benzob]thiophene-2-carbonyl)guanidine (KR-33028) in rat plasma. KR-33028 and the internal standard, linezolid, were extracted from rat plasma with ethyl acetate at neutral pH. The analytes were separated on an XBridge C(18) column with a mixture of methanol-0.1% formic acid (35:65, v/v) as mobile phase and detected using an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The standard curve was linear (r = 0.9998) over the concentration range of 2.0-1000 ng/mL. The coefficients of variation of intra- and inter-assay were 1.3-6.8% and the relative error was 0.8-5.0%. The recoveries of KR-33028 and linezolid were 70.5 and 84.6%, respectively. The lower limit of quantification for KR-33028 was 2.0 ng/mL using 50 microL plasma sample. This method was successfully applied to the pharmacokinetic study of KR-33028 in rats. |
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Keywords: | Na+/H+ exchanger inhibitor KR‐33028 rat plasma LC/MS/MS |
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