Challenges with retention and recovery of impurities containing acidic moieties during analytical UHPLC method development and validation for gefapixant freebase.

Gefapixant citrate is a P2X3 purinergic receptor antagonist developed for the treatment of chronic cough. Gefapixant freebase is the penultimate intermediate in the commercial manufacturing route for gefapixant citrate and contains a complex impurity profile consisting of acidic and basic analytes. A UHPLC method was developed for assay and purity determination of gefapixant freebase utilizing a Waters Acquity Charged Surface Hybrid (CSH) C18 column (2.