Challenging Separations: Recovery of both enantiomers of a compound with an unpredicted instability.

Client
A small, East Coast pharmaceutical firm using outsourced chemistry resources to support active discovery programs with unique biological targets.

Business Needs
Single enantiomer test articles in 20 gram quantity to be used as probes of in vivo pharmacology.

Technical Challenge
After the preparative chromatography work was under way, Averica recognized that the compound was slowly racemizing and oxidizing in its free base form. The racemic starting material, a hydrochloride salt, had been stable and useful in a previous round of pharmacology experiments.

Averica's role
Although rapid forced degradation tests with the racemate had indicated no issues, the collected eluent with each enantiomer began to turn yellow, show unidentified chromatographic peaks, and to show some conversion to the other enantiomer. Averica developed a prcedure for rapid conversion of the collected free base to the hydrochloride salt using HCL gas, and this procedure was carried out every 8 hours dring the production run. The salt was isolated as a dry white powder through a solvent exchange process developed by Averica, and repeated quality check assays showed it to be as stable as the parent racemic.

Results
The planned in vivo assays could be carried out on each isomer, allowing the lead series to continue to further development.