Challenging Separations: Bulk isolation of an unstable impurity from an API batch.

Client
A midsize, public, mid-Atlantic pharmaceutical firm with a mature product line and active dvelopment pipeline.

Business Needs
An API had an 8% process impurity with known structure that could not be isolated by conventional chromatography (silica or RP-HPLC) without decomposing. Gram quantities were required for discovery phase toxicology studies to determine the cost/benefit of developing a new process.

Technical Challenge
No chromatographic method had been developed that allowed recovery of intact material.

Averica's role
It was suspected that the compound's instability was due to reactivity with mild acid - free silanols or the water / mild acid combination often used in reversed phase chromatography. Averica's experiments with bonded phases such as CN, diol, and pyridyl modified silicas resulted in separations that proved impractical under HPLC conditions due to high solvent consumption, but were practical and scalable using supercritical fluid chromatography.

Results
Material sufficient for the desired studies was produced, and it proved stable as a dry solid compound.