Bioanalysis of INCB000928 in hemodialysate: prevention of nonspecific binding and validation of surrogate matrices.

Fibrodysplasia ossificans progressiva (FOP) is a very rare disease characterized by congenital malformation of the great toes and progressive heterotopic ossification. The genetic cause of FOP is mutation in the gene ALK2. INCB000928 is a novel and orally available drug that inhibits ALK2 protein activity and has been shown to prevent ossification in a laboratory mouse model of FOP. Patients with end-stage renal disease who undergo hemodialysis may require a different dose of INCB000928. This study showed that INCB000928 was heavily adsorbed by the container wall, resulting in underestimated drug levels in hemodialysate. We present a method to accurately measure INCB000928 levels in hemodialysate by using isopropyl alcohol as an antiadsorption agent and cost-effective surrogate matrix.