9.02 High-Throughput Analysis for High-Throughput Experimentation in Organic Chemistry

Enantioselective ultra high performance liquid and supercritical fluid chromatography: The race to the shortest chromatogram

“…the research (during drug development as an example), the separation of enantiomers could be, if too slow, a limiting step, time consuming, and costly in the whole productive process. In fact, today these processes are getting benefits from the high-throughput experiments using enabling laboratory equipment and performing many reactions per day [1][2][3][4][5][6]. For this reason, typical chromatographic analysis time of 20 min can narrow productivity.…”

“…Therefore, the improvement of chiral screening technologies and the reduced analysis time of a chromatographic separation became imperative in those areas that require continuous monitoring or real-time adaptation to changes of process. Multicolumn parallel screening and multiple injection in a single experiment run (MISER) have been employed to increase throughput when working with a large number of samples [1,[7][8][9][10]. In spite of the name, intuitively describing a simple approach, the multicolumn parallel method cannot be easily planned.…”

“…= + ∕ 0 + * 0 (1) where u 0 corresponds to the linear velocity of mobile phase (u 0 = L/t 0 , with t 0 the hold-up time), and A, B, and C correspond to eddy diffusion, longitudinal diffusion, and mass transfer resistance, respectively. However, the use of smaller particles has a direct impact on the pressure of chromatographic system according to the Darcy's equation:…”

High throughput analysis enables high throughput experimentation in pharmaceutical process research

“…We found that fast chromatographic methods coupled with mass spectrometry detection were often the best choices for such situations, although our definition of 'fast chromatography' changed dramatically over the course of this research. 71 Developing high throughput analytical methods for enzymatic transformations is generally easier than for more complex catalytic reactions containing a variety of ligands, additives and solvents. We found chromatography combined with MS detection to be a powerful tool for screening enzymatic reactions.…”

Are We Approaching a Speed Limit for the Chromatographic Separation of Enantiomers?

“…Importantly, such approaches, while offering very fast analysis speed, are often plagued by sample interference issues that are readily addressed using chromatographic separation approaches. 26 This is especially true for the analysis of enantiopurity, where suitable spectroscopic methods for high throughput enantiopurity determination that are both generally useful and interference-free are currently lacking.…”