Meeting the Challenges of Non-specific Binding in a HT-ADME Environment

An ongoing challenge when dealing with the high-throughput screening of compounds in an ADME laboratory is the presence of compounds that exhibit non-specific binding. Such compounds can accumulate within the analytical system and result in a variety of analytic issues such as:

  • Poor peak shape
  • Low sensitivity
  • Increasing back pressure/pressure spikes in the system
  • Carryover/ghost peaks
  • System clogging

These problems can get worse over time and can cause further issues for the data analyst:

  • Poor assay sensitivity
  • Poor reproducibility of data
  • Prolonged data analysis
  • Arduous method development for specific compounds

With these issues in mind, Cyprotex carried out an in-depth study examining the recent improvements in chromatographic technology introduced to address the problems described above. Of particular interest was the WatersTM Acquity Premier system (UPLC and columns). Billed as the next evolution in separation science, this system contains an inert internal coating specifically formulated to eliminate the analyte/surface interactions.

In the poster, presented at the Drug Metabolism Discussion Group (DMDG) Early Careers Meeting, we demonstrate the benefits of using the WatersTM Acquity Premier UPLC in conjunction with the Acquity Premier HSS T3 column technology in carrying out ADME screening, showcasing the improved chromatographic performance and increased sensitivity.

Compared to standard UPLC technology, the Premier UPLC platform exhibited:

  • Improved chromatographic performance
    • Sharper peaks/improved peak symmetry
    • Significant reduction in tailing
    • Better limit of detection and quantifiable peak areas
  • Rapid and efficient diagnosis for non-specific binding
  • Increased efficiency for method development work, including for peptides

Future work is planned to further examine oligonucleotide and phosphate containing compounds using the Premier system.

To read more about the work performed download the poster here.

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