A Microfluidic Platform for the Rapid Determination of Distribution Coefficients by Gravity-Assisted Droplet-Based Liquid-Liquid Extraction
A Microfluidic Platform for the Rapid Determination of Distribution Coefficients by Gravity-Assisted Droplet-Based Liquid-Liquid Extraction
复制标题
DOI：
10.1021/acs.analchem.5b01061
复制
发表时间：
2015-06-16
影响因子：
7.4
通讯作者：
Elvira, Katherine S.
中科院分区：
文献类型：
--
作者：
Poulsen, Carl Esben;Wootton, Robert C. R.;Elvira, Katherine S.
药物的药代动力学性质，如分布系数（D）的测定是药物研究中的重要测量。令人惊讶的是，用于D测量的传统（金标准）技术，摇瓶法，是过时的，不适合测试有价值的和稀缺的候选药物。在这里，我们提出了一个简单的微流控平台，用于使用液滴为基础的液液萃取的分配系数的测定。为简单起见，该平台利用重力进行相分离以进行分析，比使用摇瓶方法进行等效测量快48倍，使用的试剂少99%。此外，在我们的平台上实现的D测量与文献值测量使用传统的摇瓶技术是很好的协议。由于D受体积比的影响，我们使用表观酸解离常数pK '作为系统间比较的代表。我们的平台确定pK'值为7.24 +/- 0.15，相比之下，我们手中的摇瓶方法为7.25 +/- 0.58，文献中的摇瓶方法为7.21。使用注射成型制造装置，分批制造时间为
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