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Determination of adefovir in human plasma by liquid chromatography/tandem mass spectrometry: application to a pharmacokinetic study

Authors

  • Hui-chang Bi,

    1. Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, China
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  • Guo-ping Zhong,

    1. Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, China
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  • Shufeng Zhou,

    Corresponding author
    1. Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore
    • Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4, 18 Science Drive 4, S 117543, Singapore.
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  • Xiao Chen,

    1. Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road, Guangzhou 510080, China
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  • Min Huang

    Corresponding author
    1. Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, China
    • Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, China.
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  • Hui-chang Bi and Guo-ping Zhong contributed equally to this work.

Abstract

A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated to determine the concentrations of adefovir [9-(2-phosphonylmethoxyethyl)adenine, PMEA] in human plasma. After one-step protein precipitation of plasma samples by methanol, adefovir was analyzed by LC/MS/MS using positive electrospray ionization. Chromatography was performed on a C18 column. The extraction recoveries of adefovir were found to be 85.1–89.3%. Adefovir was stable under routine laboratory conditions. A minimal matrix effect resulting in a slight ionization enhancement of adefovir (<10.9%) was observed, which did not markedly affect the behavior of the calibrations curves and accuracy and precision data. The method had a chromatographic run time of 7.8 min and a linear calibration curve over the concentration range 1.5–90 ng/mL for adefovir. The lower limit of quantification of the method was 1.5 ng/mL. The intra- and inter-day precision was less than 8.4%. These results indicated that this LC/MS/MS method has high selectivity and efficiency, and acceptable accuracy, precision and sensitivity. The validated LC/MS/MS method has been successfully used in a pharmacokinetic study in healthy volunteers treated with oral adefovir dipivoxil at 10 and 20 mg. Copyright © 2005 John Wiley & Sons, Ltd.

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