Development of system for measurement of distribution coefficients based on flow ratiometry

流动比率法是一种专门的连续流动分析，其中两个独立交付的解决方案以不同的流量比合并。在两解汇合点下游位置监测解析信号。通过分析流量比与分析信号之间的关系，确定感兴趣的信息。本研究建立了一种快速、高通量测定药物分布系数K_D的流动比率法。得到的结果如下：1。将“体积比法”与传统的摇瓶法相结合，提出了“体积比法”作为流动比法的基础。该法成功地应用于苯酚及其相关化合物K_D的测定。采用逐级流动比法，通过逐级改变氯甲酰胺相的流动比，测定了不同化合物的K_D。相分离后测定两相中被分析物的吸光度。此外，我们开发了一种无需相分离的在线紫外检测方法，该方法将通量提高到5 min/次。建立了基于反馈的流动比率法测定酸解离常数。通过分析信号对泵速的反馈，将滴定液/滴定流比的扫描范围缩小到刚好在半等当点附近。可获得良好的通量率（26s/测定），精度高（RSD=3s）。

Flow ratiometry is a specialized continuous flow analysis, where two independently delivered solutions are merged at various flow ratios. Analytical signal is monitored at the position downstream of the confluence point of the two solutions. The information of interest is determined by analyzing the relationship between the flow ratio and the analytical signal.In this study, we developed a flow ratiometry system for the rapid and high-throughput determination of the distribution coefficients K_D of drugs. The results obtained are as follows :1.We proposed "volume ratiometry", as a basis of flow ratiometry, by combining it with conventional shake-flask method. The method was successfully applied to the determination of K_D of phenol and its relation compounds.2.The K_D of various compounds was determined based on stepwise flow ratiometry, where the flow ratio of chloroformlaqueous phases were changed stepwise. The absorbance of analyte in either of the phases was measured after the phase separation. Further, we developed an on-line UV detection method without phase separation, which improved the throughput rate up to 5 min/determination.3.Feedback-based flow ratiometry was developed for the determination of acid dissociation constants. The scan range of titrant/titrand flow ratio was narrowed down to just the vicinity of the half equivalence point by the feedback of analytical signal to pump speed. Good throughput rate (26s/determination) was attainable with good precision (RSD=3s).