New horizons in small molecule solubility screening

Supported by:

21 November 2019

Supported by:

21 November 2019


Aqueous solubility of small molecule compounds is an essential parameter during the hit-to-lead stage of drug discovery as well as lead optimization and formulation. Low solubility can result in misleading ADMET/DMPK analyses if some fraction of a compound precipitates. Poor bioavailability and underestimated toxicity can increase development costs and reduce the chances of a drug candidate’s success. Despite its critical importance at early stages, commonly used methods to measure solubility are either inefficient (filtration + LC-MS), lack sensitivity (light scattering/turbidimitry) or are subject to interference from matrix and impurities (UV spectroscopy). Here we introduce Backgrounded Membrane Imaging (BMI), an automated microscopy technology that rapidly images and counts insoluble subvisible aggregates in low-volume, high throughput format. We demonstrate use of BMI on the HORIZON system for straightforward, reliable kinetic solubility determination with greater sensitivity than turbidimitry. Analysis is high throughput, requires as little as 30ul of sample and is insensitive to solvent or media interference -making it ideal for quick identification of problematic candidates in early stage screening. Unlike other methods, particle image analysis provides useful information on solid state morphology for more comprehensive solubility characterization.

Key learning points:

  • Explore a novel method for high throughput solubility screening in drug discovery that is easy to use and insensitive to solvent or matrix interference
  • Discover how BMI technology can accelerate pre-ADMET solubility workflow
  • Learn how particle imaging can provide useful information about compound solid state characteristics.


Gabriel Mercado, PhD, Senior Marketing Applications Scientist, Halo Labs

Gabriel Mercado, PhD

Dr Mercado has been conducting discovery efforts in the field of drug discovery, structural biology and the screening of combinatorial libraries for multiple therapeutic areas for over 20 years; carrying out his research at both prestigious academic and biotech institutions. Dr Mercado’s research activities show a great diversity and strong interest for new tools, applications and technologies applied to the discovery and development of new therapeutic agents and targets both from a user and an inventor standpoint.

Dr Mercado is currently working with Halo Labs to find better systems to inform, evaluate and guide drug discovery efforts.

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