KMID : 0369820090390050367
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Jorunal of Korean Pharmaceutical Sciences 2009 Volume.39 No. 5 p.367 ~ p.372
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Rapid Quantification of Topotecan in Biological Samples by Liquid Chromatography/Tandem Mass Spectrometry
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Shin Beom-Soo
Lee Mann-Hyung Yoo Sun-Dong
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Abstract
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A rapid liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay method was developed for the determination of topotecan levels in rat serum. The assay utilized a single liquid-liquid extraction with a mixture of ethy l acetate and acetonitrile (6:1 v/v) and isocratic elution. The multiple reaction monitoring was based on the transition of m/z 422.0376.5 for topotecan and 315.1226.6 for clomipramine (internal standard). The developed assay was validated to demonstrate the specificity, recovery, lower limit of quantification (LLOQ), accuracy and precision. The assay was linear over a concentration range from 0.5-100 ng/mL, with LLOQ being 0.5 ng/mL using a small volume of rat serum (0.1 mL). The mean intra- and inter-day assay accuracy was 87.7-111.0% and 97.8-108.3, respectively, and the mean intra- and interday precision was between 1.6-4.3% and 3.8-10.3, respectively. The developed assay was applied to a pharmacokinetic study after a bolus i.v. injection of topotecan in rats.
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KEYWORD
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Topotecan, LC/MS/MS, Clomipramine, Pharmacokinetics
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