Micro Parallel Liquid Chromatography for High-Throughput Compound Purity Analysis and Early ADMET Profiling

Abstract

The Nanostream (Pasadena, CA) Veloce system, together with 24-column Brio cartridges, offers a novel approach to micro parallel liquid chromatography (μPLC). This system allows users to achieve unprecedented throughput for standard assays while matching the performance of conventional LC instrumentation, thus enabling routine compound purity assessment and physiochemical property profiling early in the drug discovery and development process. The Veloce system—which includes instrumentation, software, and replaceable microfluidic cartridges—incorporates pressure-driven flow to achieve chromatograms comparable to conventional high performance liquid chromatography (HPLC) instrumentation for a broad class of analytical applications while offering a dramatic increase in sample analysis capacity. The system enables parallel chromatographic separations and simultaneous, real-time UV detection. Each Nanostream Brio cartridge, made of polymeric materials, incorporates 24 columns packed with standard (C-18) stationary phase material to achieve reverse phase separations. Mixing and distribution of the mobile phase to each of the 24 columns is precisely controlled in each cartridge. The system provides an ideal platform to accelerate assessment of compound purity and physicochemical properties (i.e., log P, CHI, etc.) for a large number of compounds. In addition, the 24-fold increase in sample analysis capacity allows standard curve generation and simultaneous analysis of multiple replicates of samples in a single run. (JALA 2004;9:185-91)

Development and Application of an Automated Solution Stability Assay for Drug Discovery

“…One solution to this may be multichannel analysis systems that simultaneously analyze 24 samples. 21 This would allow studies of solution stability for 24 compounds or 24 buffer conditions at the same time, but most labs do not have this instrumentation. However, many labs do have automated HPLC and LC-MS systems, such as those used for drug development studies, combinatorial synthesis monitoring, and bioanalysis.…”