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Parallel artificial liquid membrane extraction of acidic drugs from human plasma

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Abstract

The new sample preparation concept “Parallel artificial liquid membrane extraction (PALME)” was evaluated for extraction of the acidic drugs ketoprofen, fenoprofen, diclofenac, flurbiprofen, ibuprofen, and gemfibrozil from human plasma samples. Plasma samples (250 μL) were loaded into individual wells in a 96-well donor plate and diluted with HCl to protonate the acidic drugs. The acidic drugs were extracted as protonated species from the individual plasma samples, through corresponding artificial liquid membranes each comprising 2 μL of dihexyl ether, and into corresponding acceptor solutions each comprising 50 μL of 25 mM ammonia solution (pH 10). The liquid membranes and the acceptor solutions were located in a 96-well filter plate, which was sandwiched with the 96-well donor plate during extraction. Parallel extraction of several samples was performed for 15 to 60 min, followed by high-performance liquid chromatography-ultraviolet detection of the individual acceptor solutions. Important PALME parameters including the chemical composition of the liquid membrane, extraction time, and sample pH were optimized, and the extraction performance was evaluated. Except for flurbiprofen, exhaustive extraction was accomplished from plasma. Linearity was obtained for all six drugs in the range 0.025–10 μg/mL, with r 2 values ranging between 0.998 and 1.000. Precision data were in the range 3–22 % RSD, and accuracy data were within 72–130 % with spiked plasma samples. Based on the current experiences, PALME showed substantial potential for future high-throughput bioanalysis of non-polar acidic drugs.

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Acknowledgments

The authors want to thank the Research Council of Norway for the support of parts of this project (NFR 234396). M. Roldán-Pijuán wishes to thank the Ministry for the award of a FPU Research Training Fellowship (Grant AP2009-3499), and gratefully acknowledges funding of her stay in Oslo at the School of Pharmacy to conduct the research reported in this paper.

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Authors and Affiliations

  1. Department of Analytical Chemistry, Institute of Fine Chemistry and Nanochemistry, University of Córdoba, Marie Curie Building, Campus de Rabanales, 14071, Córdoba, Spain

    Mercedes Roldán-Pijuán

  2. School of Pharmacy, University of Oslo, PO Box 1068 Blindern, 0316, Oslo, Norway

    Stig Pedersen-Bjergaard & Astrid Gjelstad

  3. School of Pharmaceutical Sciences, Faculty of Health & Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark

    Stig Pedersen-Bjergaard

Authors
  1. Mercedes Roldán-Pijuán
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  2. Stig Pedersen-Bjergaard
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  3. Astrid Gjelstad
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Corresponding author

Correspondence to Astrid Gjelstad.

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Roldán-Pijuán, M., Pedersen-Bjergaard, S. & Gjelstad, A. Parallel artificial liquid membrane extraction of acidic drugs from human plasma. Anal Bioanal Chem 407, 2811–2819 (2015). https://doi.org/10.1007/s00216-015-8505-9

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  • DOI: https://doi.org/10.1007/s00216-015-8505-9

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