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Testing the boundaries in LC-MS – Application of Ultra-fast LC-MS to High Throughput ADME Screening

Improving efficiency is essential to reduce the timelines and ultimately cost associated with the drug discovery and development process. Most ADME assays require sample analysis by LC-MS/MS, which can be a time limiting factor and act as a bottleneck in this process. To address this bottleneck, there has been a push to improve cycle time through advances in both liquid chromatography and mass spectrometry.

High resolution accurate mass (HRAM) mass spectrometry has played an important role in advancing sample analysis speed by eliminating the need for MS optimisation. Rapid scanning speeds have enabled large amounts of data to be collected over short time frames allowing quality to be maintained even when relatively fast cycle times are applied. In terms of liquid chromatography, UPLC/UHPLC (ultra high performance liquid chromatography) has been developed through reduction in the column particle size requiring the system to run at higher pressure but providing improved chromatographic resolution, sensitivity and speed.

Adding to the techniques described above, Cyprotex have evaluated further enhancements by using very short columns attached directly to the MS ion source to minimise post-column volume. Combined with higher flow rates this has allowed cycle times to be further reduced. The validation of this ultra-fast LC-MS system compared chromatographic and data quality against a more conventional  column length/run time using standard column chemistry. The ultra-fast system achieved 4 x faster run times than the more conventional method with comparable data quality. Performance of the systems included measures of peak broadness, tailing factors, sensitivity, matrix effects, linearity, reproducibility and robustness with time.

The results from the study were presented in a poster at HT-ADME in Boston on July 20th, 2019.

Download the poster

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