WHAT IS BIOMIMETIC CHROMATOGRAPHY ?

​​How it works

Bio-mimetic chromatography is the use of human proteins and phospholipid to model the in vivo distribution of compounds.  Commercially available HPLC columns containing immobilised human serum albumin (HSA), immobilised artificial membrane (IAM) and immobilised alpha-1-acid-glycoprotein (AGP), act as biorelevant stationary phases.

As mobile phases containing the compounds pass through the column, the retention time of a compound is directly proportional to its affinity/dynamic equilibrium with the relevant stationary phase.

Combination of the measurements (retention times) of these three stationary phases provides accurate estimation of a compound's affinity for each human non-specific binding components, and therefore their in vivo distribution.



Biomimetic chromatography allows the optimisation of candidate selection leading to:
  • Reduced animal testing
  • ​Reduced costs
  • ​Reduced late stage attrition
  • Early dose estimation

​Biomimetic stationary phases:

Importance

The information provided is very valuable when moving forward a drug discovery project. It allows a better candidate selection, accounting for distribution, as well as efficacy.

In vivo distribution is a vital parameter as it defines the amount of free drug available to have an efficacious effect. High volume distribution means the drug readily binds to non-specific sites in tissues. When the compound also binds strongly to plasma proteins, these all act to reduce the free drug concentration and subsequently, efficacy. High volume of distribution has also shown links to the increased possibility of toxicity.

Biomimetic chromatography is a quick, easy and cost effective method that allows researchers to better understand their candidates' in vivo distribution. This means only compounds with a good in vivo profile will move forward to costly animal testing.

Biomimetic chromatography therefore allows the optimisation of candidate selection, meaning fewer costly animal tests on compounds likely to fail due to poor efficacy or toxicity. More information on drug efficiency can help to optimise dosing regimens.

In addition, unlike an octanol/water partition, biomimetic chromatography is based on human body components and accounts for shape and differentiates charge specificity.

​​Biomimetic Chromatography provides predictions of: