This paper describes the development of a simple reversed-phase HPLC method that can quantitate trace amounts of a polymeric degradants (BMT-041910) in asunaprevir drug substance and formulated drug product with quantitation limits of ˜0.05% w/w. The method has overcome several challenges of polymer quantitation such as band broadening, peak coeluting and low sensitivity. The hydrophobic function group (BOC) of BMT-041910 is removed to increase its aqueous solubility by a simple sample treatment procedure (des-BOC). The des-BOC polymer (BMT-052076) is excluded from stationary phase pores and eluted as a single peak before solvent front, and then its peak area response can be used to determine BMT-041910 amount. The HPLC conditions were optimized using a 250 × 4.6 mm Waters XSelect CSH column maintained at 30 °C with a mobile phase of water-acetonitrile-trifluoroacetic acid (20:80:0.1 v/v/v). The feasibility of other HPLC approaches including size exclusion chromatography and normal phase chromatography were also investigated and found to be less suitable for this particular application. Validation data for this method in terms of precision, linearity, accuracy and sensitivity are also presented.