Enabling Faster Separations and Smaller Sample Volumes with Micro-flow Liquid Chromatography

摘要

Microflow LC-MS with column diameters <=1mm is proving to be a valuable approach for high-throughput LC-MS in bioanalytical development, including ADME-Tox measurements. We recently described a chromatography system designed for this application that allows very fast separations (1 to 1.5 minute cycle times). The system can deliver fast and accurate gradients at flow rates below 200 uL/min with very low gradient delays and fast re-equilibrations. In addition to fast, high performance separations, high-throughput LC-MS workflows also require low carryover and fast injection-to-injection cycle times. Additional benefits of microflow LC-MS can also be realized by efficiently injecting from limited sample volumes. Studies involving single animal pharmacokinetic profiles and sampling with dried blood/matrix spots are two examples of workflows that can benefit from small sample volume analyses. In this study we examine the use of a new autosampler injection system with modifications for small volume handling that allows for low carryover and sub-minute cycle times using microflow LC-MS. In addition, modified probes have been developed and tested that provide high performance coupling of these microflow separations to the electrospray source.