Analysis of a polydisperse heparin analog therapeutic (CX-01, Dociparstat) was conducted in human plasma by signature disaccharide (NS6S) analysis, with NS6S being unique to CX-01 in native human plasma but common to the concomitantly dosed low molecular weight heparin (LMWH), Enoxaparin, in COVID-19 patients, demonstrating a novel quantification approach to concomitant related glycosaminoglycan (GAG) therapeutics. Signature disaccharide response correction was required to achieve accurate Dociparstat quantification in concomitantly dosed samples by in-run monitoring of an alternate signature disaccharide unique to the LMWH. The method was used to determine CX-01 concentrations in a Phase 2/3 study to evaluate the safety and efficacy of Dociparstat sodium for the treatment of severe COVID-19 in adults at high risk of respiratory failure.