A Microfluidic Platform for the Rapid Determination of Distribution Coefficients by Gravity-Assisted Droplet-Based Liquid–Liquid Extraction
Date
2015
Authors
Poulsen, Carl Esben
Wootton, Robert C. R.
Wolff, Anders
deMello, Andrew J.
Elvira, Katherine S.
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Publisher
Analytical Chemistry
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 microfluidic 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 intersystem 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 the literature. Devices are fabricated using injection molding, the batchwise fabrication time is <2 min per device (at a cost of $1 U.S. per device), and the interdevice reproducibility is high.
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Citation
Poulsen, C.E., Wootton, R.C.R., Wolff, A., deMello, A.J. & Elvira, K.S. (2015). A Microfluidic Platform for the Rapid Determination of Distribution Coefficients by Gravity-Assisted Droplet-Based Liquid–Liquid Extraction. Analytical Chemistry, 87(12), 6265–6270. https://doi.org/10.1021/acs.analchem.5b01061