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Simultaneous Quantification of Benazepril, Gliclazide and Valsartan in Human Plasma by LC–MS–MS and Application for Rapidly Measuring Protein Binding Interaction between Rhein and These Three Drugs

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Abstract

For new drug candidates with high protein binding in the treatment of diabetic nephropathy, their influence on the protein bindings of angiotensin-converting enzyme inhibitors, sulfonylurea drugs, and angiotensin receptor blockers should be predicted to prevent side effects. To provide an efficient tool for this study, a sensitive and rapid LC–MS–MS method was developed for the simultaneous quantification of representative drugs, benazepril, gliclazide and valsartan in human plasma. Chromatographic separation was performed on a Shim-pack VP-ODS C18 column (250 × 2.0 mm i.d., 5 μm) using methanol–0.05% formic acid (90:10, v/v) as mobile phase. Detection was performed on a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization source and operated in SRM mode. Lower limits of quantification were 2, 2 and 20 ng−1 mL for benazepril, gliclazide and valsartan with 0.1 mL plasma sample. The method fulfills the precision, accuracy, linearity, sensitivity, selectivity requirements to quantify the three drugs and has been successfully used to studying protein binding of benazepril, gliclazide and valsartan in the presence of rhein.

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Acknowledgments

We greatly thank Professor Sun Fenzhi for kind assistance in the revision of the paper. This study was supported by National “863” Project (No. 2003AA2Z347A, 2005AA2Z3C70, 2002AA2Z3113).

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Authors and Affiliations

  1. Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24 Tong Jia Xiang Street, 210009, Nanjing, China

    Xiaoling Hu, Yuanting Zheng, Jianguo Sun, Lili Shang & Guangji Wang

  2. Research Institution of Nephrology, Jinling Hospital, Nanjing University School of Medicine, 210002, Nanjing, China

    Haitao Zhang

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  1. Xiaoling Hu
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  2. Yuanting Zheng
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  3. Jianguo Sun
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  4. Lili Shang
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  5. Guangji Wang
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  6. Haitao Zhang
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Correspondence to Guangji Wang.

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Hu, X., Zheng, Y., Sun, J. et al. Simultaneous Quantification of Benazepril, Gliclazide and Valsartan in Human Plasma by LC–MS–MS and Application for Rapidly Measuring Protein Binding Interaction between Rhein and These Three Drugs. Chroma 69, 843–852 (2009). https://doi.org/10.1365/s10337-009-1017-z

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