A microfluidic platform for the rapid determination of distribution coefficients by gravity assisted droplet-based liquid-liquid extraction

Carl Esben Poulsen, Robert C. R. Wootton, Anders Wolff, Andrew J. deMello, Katherine S. Elvira

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    Abstract

    The determination of pharmacokinetic properties of drugs, such as the distribution coefficient, D, is a crucial measurement in pharmaceutical research. Surprisingly, the conventional (gold standard) technique used for D measurements, the shake-flask method, is antiquated and unsuitable for the testing of valuable and scarce drug candidates. Herein we present a simple micro fluidic platform for the determination of distribution coefficients using droplet-based liquid-liquid extraction. For simplicity, this platform makes use of gravity to enable phase separation for analysis and is 48 times faster and uses 99 % less reagents than performing an equivalent measurement using the shake-flask method. Furthermore, the D measurements achieved in our platform are in good agreement with literature values measured using traditional shake-flask techniques. Since D is affected by volume ratios, we use the apparent acid dissociation constant, pK', as a proxy for inter-system comparison. Our platform determines a pK' value of 7.24 ± 0.15, compared to 7.25 ± 0.58 for the shake-flask method in our hands and 7.21 for the shake-flask method in literature. Devices are fabricated using injection moulding, the batch-wise fabrication time is less than 2 minutes per device (at a cost of 1 USD per device) and the inter-device reproducibility is high.
    Original languageEnglish
    JournalAnalytical Chemistry
    Volume87
    Issue number12
    Pages (from-to)6265-6270
    Number of pages6
    ISSN0003-2700
    DOIs
    Publication statusPublished - 2015

    Keywords

    • Bottles
    • Dissociation
    • Drops
    • Injection molding
    • Liquids
    • Microfluidics
    • Phase separation
    • Solvent extraction
    • Acid dissociation constants
    • Distribution coefficient
    • Equivalent measurement
    • Liquid-liquid extraction
    • Microfluidic platforms
    • Pharmaceutical research
    • Pharmacokinetic properties
    • Shake-flask method
    • Extraction

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