Pharmacelsus – Success Story 2

Reliable protein binding measurement even for critical compounds

Challenge

Pharmacelsus was challenged to determine plasma protein binding of a peptidic NCE. According to the customer, determination of plasma protein binding of this compound failed in labs of other CROs.

First Steps

Initial experiments applying the standard ultrafiltration technique led to the conclusion that the NCE was a high binder to plasma proteins and was also susceptible to non-specific binding to the polymer-based components of the filter devices. Thus accurate determination of plasma protein binding by routine set-ups was not applicable.

Idea

Following intensive literature research (free of charge for the client), Pharmacelsus set up a modified ultrafiltration method to determine plasma protein binding. While standard ultrafiltration techniques only foresee the measurement of the NCE content in the filtrate, i.e. the unbound fraction, the modification of the method allowed the quantification of the bound fraction in the retentate and thus the calculation of recovery of the NCE from the system.

Results

It could be demonstrated that by modification of the ultrafiltration method, recovery of the NCE could be significantly improved and allowed a reliable and robust determination of the plasma protein binding capacity of the peptidic NCE in a consistent matrix.

Since then the new modified ultrafiltration method has been used for many high binding compounds and revealed reliable data on plasma protein binding of these compounds.

Perhaps it is not about getting the fastest CRO, but about getting results from a CRO, who is on the front lines of assay development!