Bio Mimetic Chromatography

  • Physchem & biomimetic HPLC measurement Stevenage, Hertfordshire, UK
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The Method

How it works

Bio-Mimetic Chromatography uses calibrated HPLC retention measurements to quantify molecular properties that determine the in vivo distribution of drug-discovery compounds.

The standard platform comprises six chromatographic measurements:

• C18 reversed-phase chromatography at three pH values, providing chromatographic lipophilicity information for different ionisation states
• IAM (immobilised artificial membrane) chromatography, measuring phospholipid/membrane affinity
• HSA chromatography, measuring human serum albumin binding
• AGP chromatography, measuring α1-acid glycoprotein binding

As compounds pass through these columns, their retention reflects their interactions with the corresponding stationary phase. Calibration converts retention times into quantitative physicochemical and biomimetic property data.

These experimentally measured properties are then combined in 22 predictive models to estimate important ADMET and in vivo distribution parameters.

Experimental measurements translated into in vivo predictions

3 × pH CHI
Protein binding
Phospholipid binding
In vivo distribution behaviour
Plasma Protein Binding
Measures how compounds bind to Human Serum Albumin (HSA) and Alpha-1-Acid Glycoprotein (AGP) using HPLC columns, giving accurate free-fraction data without the recovery loss, non-specific binding, or equilibrium time issues seen in traditional equilibrium dialysis.
Volume of Distribution
Uses experimental phospholipid and protein binding parameters to calculate physiological volume of distribution, indicating whether a drug stays in blood plasma or distributes heavily into tissues.
Blood–Brain Distribution
Predicts brain tissue exposure and brain-to-plasma ratios by evaluating membrane permeability and binding affinity, helping identify CNS-active candidates or screen out central side effects.
Tissue Binding
Quantifies specific membrane partitioning (using Immobilized Artificial Membrane columns) to predict non-specific binding across organ tissues without requiring animal tissue homogenates.
Intracellular Concentration
Models how drugs cross cell membranes and accumulate inside cells or sub-cellular compartments (like lysosomes) driven by pH gradients and phospholipid interactions.
Drug Efficiency
Derives Lipophilic Efficiency (LipE) and Ligand Efficiency indices by comparing chromatographic lipophilicity against target potency, guiding leads toward optimal activity without unnecessary lipophilicity.
Dose-Related Predictions
Combines biomimetic parameters to estimate early human dose requirements, systemic clearance trends, and oral absorption potential long before entering expensive animal or clinical trials.
Phospholipidosis & Other Safety-Related Applications
Flags potential drug safety issues early by detecting high phospholipid retention, which serves as a biomarker for drug-induced phospholipidosis and membrane toxicity risk.
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