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Simultaneous Determination of Deoxypodophyllotoxin and Its Major Metabolites in Rat Plasma by a Sensitive LC–MS/MS Method and Its Application in a Pharmacokinetic Study

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Abstract

The purpose of this study is to develop and validate a rapid and sensitive liquid chromatography-tandem mass spectrometry method for the quantification of deoxypodophyllotoxin (DPT) and its major metabolites (M1, M2, M7) in rat plasma. Diazepam was used as the internal standard. The method involves a simple liquid–liquid extraction with ethyl acetate. Chromatographic separation was accomplished on a Shim-pack VP-ODS analytical column (2.0 mm × 150 mm, 5 μm) with gradient elution using a mobile phase consisting of acetonitrile and water (containing 0.1 % formic acid) at a flow rate of 0.2 mL min−1. The detection was performed by multiple reaction monitoring mode via a positive electrospray ionization interface. The calibration curves were linear for all analytes over investigated range. The lower limits of quantification were 7.734 ng mL−1 for DPT, 1.973 ng mL−1 for M1, 7.969 ng mL−1 for M2, and 1.973 ng mL−1 for M7, respectively. The intra- and inter-day precision values were less than 10.59 %, and the accuracy ranged from −6.787 to 12.74 %. The extraction recoveries of the analytes were higher than 90 % and in this method no apparent matrix effect was observed. The validated method was successfully applied to pharmacokinetic study of DPT and its main metabolites in rat plasma.

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Acknowledgments

The project was supported by the National Science foundation of China (No. 81473273, No. 81373482, and No. 81573490), the Fundamental Research Funds for the Central Universities (2015PT042, ZD2014YX0026, PT2014YX0057), the Priority Academic Program Development of Jiangsu Higher Education Institutions, and the policy directive program of Jiangsu Province (BY2015072-03).

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  1. Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, 210009, China

    Fei Liu, Yang Chen, Qiushi Xie, Li Liu, Ping Xu, Zeyu Zhong & Xiaodong Liu

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  1. Fei Liu
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  2. Yang Chen
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  3. Qiushi Xie
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  4. Li Liu
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  5. Ping Xu
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  6. Zeyu Zhong
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  7. Xiaodong Liu
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Correspondence to Xiaodong Liu.

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Liu, F., Chen, Y., Xie, Q. et al. Simultaneous Determination of Deoxypodophyllotoxin and Its Major Metabolites in Rat Plasma by a Sensitive LC–MS/MS Method and Its Application in a Pharmacokinetic Study. Chromatographia 79, 53–61 (2016). https://doi.org/10.1007/s10337-015-2992-x

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  • DOI: https://doi.org/10.1007/s10337-015-2992-x

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