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T.J. Higley and Roy Eksteen, Tosoh Bioscience LLC, Montgomeryville, Pennsylvania and Scott Lauder, Lexigen Pharmaceuticals, Lexington, Massachusetts
Introduction:
During method development, many variables are examined to ensure method
robustness. Factors such as elution profile, peak shape, and recovery
are required to be consistent by GMP/GLP protocols. During a recent method
re-qualification at Lexigen Pharmaceuticals, several variables were investigated
to eliminate non-specific binding and increase the robustness of an established
antibody separation method. Previous protocol required an unacceptable
two-week "break-in" period to equilibrate the column with the mobile phase.
Reduction of non-specific binding of proteins to SEC stationary phases
can be achieved by exploring variables that affect either the ionic strength
or hydrophobicity of the mobile phase. Typically, changes in mobile phase
composition, such as buffer type and pH, salt concentration, the addition
of organic modifiers, as well as the evaluation of competitive columns
are the usual strategies to correcting non-specific adsorption. In this
case, these options did not result in an improvement. Thus, an alternative
approach to increase the chaotropic nature of the mobile phase was investigated.
Concurrently, the buffer concentration was reduced to a minimum buffering
capacity and the modifying salt was changed to NaClO4. A drastic
improvement on the performance of the method was evident.
Experimental Conditions:
Gel filtration was performed with a 4.6mmID x 30cm TSKgel Super SW3000
column packed with 4m particles containing 250 pores. The original
run
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