Challenging Separations: Removal of an otherwise inseparable regioiosmer from a drug candidate

Client
A midsize, public, East Coast pharmaceutical firm with a mature discovery/development team but with no in-house SFC equipment.

Business Needs
A lead optimization candidate needed at the gram scale for several assays could not be isolated from a 9% impurity.

Technical Challenge
The impurity was identified by the client company as a regioisomer through analytical scale chromatography using a chiral stationary phase. The challenge was to develop a scalable SFC method on any medium that allowed purification. The client was also interested in capturing the impurity for competitive screening.

Averica's role
Averica found the impurity was separable on two chiral phases, but only loaded well on one. A rapid forced degradation study indicated the compound was stable in the selected mobile phase, which contained small amounts of isopropylamine. Method development took 1 day. 3.0 g of the mixture was purified in 8 hours - a low production rate required by the limited separation, a = 1.2

Results
Toxicology and functional assays could be carried out on each isomer, both increasing the quality of the assay data and the quality of the series SAR results.