ARC Training Centre for Portable Analytical Separation Technologies (ASTech), School of Natural Sciences, University of Tasmania, Private Bag 75, Hobart, Tasmania 7001, Australia; Australian Centre for Research on Separation Science (ACROSS), School of Natural Sciences, University of Tasmania, Private Bag 75, Hobart, Tasmania 7001, Australia.
ARC Training Centre for Portable Analytical Separation Technologies (ASTech), School of Natural Sciences, University of Tasmania, Private Bag 75, Hobart, Tasmania 7001, Australia; Trajan Scientific and Medical, 7 Argent Place, Ringwood, Victoria 3134, Australia.
J Chromatogr A. 2021 Oct 25;1656:462545. doi: 10.1016/j.chroma.2021.462545. Epub 2021 Sep 10.
Liquid chromatography (LC) has broad applicability in the pharmaceutical industry, from the early stages of drug discovery to reaction monitoring and process control. However, small footprint, truly portable LC systems have not yet been demonstrated and fully evaluated practically for on-line, in-line or at-line pharmaceutical analysis. Herein, a portable, briefcase-sized capillary LC fitted with a miniature multi-deep UV-LED detector has been developed and interfaced with a portable mass spectrometer for on-site pharmaceutical analysis. With this configuration, the combined small footprint portable LC-UV/MS system was utilized for the determination of small molecule pharmaceuticals and reaction monitoring. The LC-UV/MS system was interfaced directly with a process sample cart and applied to automated pharmaceutical analysis, as well as also being benchmarked against a commercial process UPLC system (Waters PATROL system). The portable system gave low detection limits (∼3 ppb), a wide dynamic range (up to 200 ppm) and was used to confirm the identity of reaction impurities and for studying the kinetics of synthesis. The developed platform showed robust performance for automated process analysis, with less than 5.0% relative standard deviation (RSD) on sample-to-sample reproducibility, and less than 2% carryover between samples. The system has been shown to significantly increase throughput by providing near real-time analysis and to improve understanding of synthetic processes.
液相色谱（LC）在制药行业具有广泛的适用性，从药物发现的早期阶段到反应监测和过程控制。然而，小体积、真正便携的 LC 系统尚未得到实际展示和全面评估，无法用于在线、在线或在线制药分析。在此，开发了一种便携式公文包大小的毛细管 LC，配备了微型多深紫外-LED 检测器，并与便携式质谱仪接口，用于现场制药分析。通过这种配置，组合的小体积便携式 LC-UV/MS 系统用于小分子药物的测定和反应监测。LC-UV/MS 系统直接与过程样品推车接口，并应用于自动化制药分析，同时与商业过程 UPLC 系统（Waters PATROL 系统）进行基准测试。该便携式系统具有较低的检测限（约 3 ppb）、较宽的动态范围（高达 200 ppm），用于确认反应杂质的身份和研究合成动力学。所开发的平台在自动化过程分析中表现出稳健的性能，在样品间重现性方面的相对标准偏差（RSD）小于 5.0%，在样品间的残留小于 2%。该系统通过提供近实时分析，显著提高了分析通量，并有助于加深对合成过程的理解。
