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首页> 外文期刊>Journal of chromatography, B. Analytical technologies in the biomedical and life sciences >Simultaneous determination of dronedarone and its active metabolite debutyldronedarone in human plasma by liquid chromatography-tandem mass spectrometry: Application to a pharmacokinetic study
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Simultaneous determination of dronedarone and its active metabolite debutyldronedarone in human plasma by liquid chromatography-tandem mass spectrometry: Application to a pharmacokinetic study

机译：液相色谱-串联质谱法同时测定人血浆中决奈达隆及其活性代谢物去丁基决酮达隆：在药代动力学研究中的应用

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摘要

Dronedarone is a derivative of amiodarone - a popular antiarrhythmic drug. It was developed to overcome the limiting iodine-associated toxicities of amiodarone. Debutyldronedarone is a major circulating active metabolite of dronedarone in humans. To investigate the pharmacokinetics of dronedarone, a rapid, simple, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine dronedarone and debutyldronedarone in human plasma using amiodarone as internal standard (IS). Acetonitrile with IS was used to precipitate proteins from a 50-μL aliquot of plasma. Effective chromatographic separation was performed on a CAPCELL PAK C_(18) MG (100mm×4.6mm, 5μm) column with gradient elution (5mmol/L ammonium acetate-acetonitrile, with each phase containing 0.2% acetic acid) at a flow rate of 0.7mL/min. Complete separation was achieved within 5.5min. Detection was carried out on an tandem mass spectrometer in multiple reaction monitoring mode using a positive atmospheric pressure chemical ionization interface. A lower limit of quantification of 0.200ng/mL was achieved for both dronedarone and debutyldronedarone, with acceptable precision and accuracy. The linear range of the method was from 0.200 to 200ng/mL for each analyte. Intra- and inter-day precisions were lower than 7.2% in relation to relative standard deviation, while accuracy was within ±5.1% in terms of relative error for analytes. Our findings demonstrate the successful application of the validated LC-MS/MS method to a pharmacokinetic study after a single oral administration of 400mg dronedarone to six healthy volunteers.
机译：决奈达隆是一种流行的抗心律不齐药物胺碘酮的衍生物。开发它是为了克服碘碘酮与碘有关的有限毒性。脱氢丁烯酮是人类决奈达隆的主要循环活性代谢产物。为了研究决奈达隆的药代动力学，开发了一种快速，简单且灵敏的液相色谱-串联质谱（LC-MS / MS）方法，并验证了使用胺碘酮作为内标（IS）同时测定人血浆中的决奈达隆和去丁基决奈达隆。带有IS的乙腈用于从等分的50μL血浆中沉淀蛋白质。在CAPCELL PAK C_（18）MG（100mm×4.6mm，5μm）色谱柱上进行有效色谱分离，梯度洗脱（5mmol / L乙酸铵-乙腈，每相均含0.2％乙酸），流速为0.7毫升/分钟5.5分钟内完全分离。使用正大气压化学电离界面，在多反应监测模式下，在串联质谱仪上进行检测。决奈达隆和去甲基丁达隆达的定量下限均为0.200ng / mL，精密度和准确性均可接受。对于每种分析物，该方法的线性范围为0.200至200ng / mL。日间和日间精度相对于相对标准偏差低于7.2％，而就分析物的相对误差而言，其精度在±5.1％以内。我们的发现表明，对六名健康志愿者单次口服400mg决奈达隆后，已成功将经过验证的LC-MS / MS方法应用于药代动力学研究。

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