Selecting The Right Chromatography Strategy For Difficult-To-Purify Small Molecules

A closely eluting impurity that stalls at 0.2 area% against a specification below 0.1. An unstable molecule, and lyophilization capacity for only six fractions. A starting purity of roughly 73%. Each of these purification problems with ADC linker-payloads called for a different chromatography answer, and none was solved by applying one technique across the board. Three examples from Benjamine Hale's process development team show how digital modeling, fraction mapping, and preparative HPLC were each chosen for a specific reason. They also look at what each approach costs in material, solvent, analytical effort, and operational complexity.

Examine the data behind each decision and see how the tradeoffs were weighed.