A Microfluidic Platform for the Rapid Determination of Distribution Coefficients by Gravity-Assisted Droplet-Based Liquid-Liquid Extraction

Anal Chem. 2015 Jun 16;87(12):6265-70. doi: 10.1021/acs.analchem.5b01061. Epub 2015 May 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Liquid-Liquid Extraction*
  • Microfluidic Analytical Techniques* / instrumentation
  • Particle Size
  • Quinine / analysis*
  • Surface Properties

Substances

  • Quinine