Scientific Poster , Bioanalysis

EBF 2021: Novel Copper Protein Speciation Method for Calculating Serum Non Ceruloplasmin Copper: A Comparative Analysis


Download Quotient Sciences' poster, 'EBF 2021: Novel Copper Protein Speciation Method Calculating Serum Non-Ceruloplasmin Copper: A Comparative Analysis'.

  • Wilson disease (WD) is an autosomal recessive disorder of copper (Cu) transport caused by mutations of the ATP7B gene
  • International guidelines on the management of WD recommend serum non-ceruloplasmin-bound Cu (NCC; free Cu index) for diagnosis and therapeutic monitoring; NCC target range in WD = 50 to 150μg/L
  • The current “Standard of Care” evaluation of NCC levels involves the incubation of serum with EDTA (NCC-EDTA) to chelate copper from proteins other than ceruloplasmin before ultracentrifugation
  • A high molecular weight artifact binding copper from albumin retained above the 30KDa filter may result in an underestimation of true NCC
  • During the conduct of an RCT (clinical trials gov: NCT03539952), the FDA highlighted the deficiencies in NCC-EDTA
  • Orphalan developed and optimized a novel assay to determine NCC using copper protein speciation (NCC-CuSp) with LC-ICP-MS
  • The NCC-CuSpassay is a two-step process that involves:
  • Inductively coupled mass spectrometry to measure total Cu
  • Liquid chromatography (LC-ICP-MS) to calculate Cp-Cu as a percentage of total Cu
  • LC-ICP-MS determines Cp-Cu indirectly by the speciation of Cu-containing proteins
  • There are no data in WD subjects comparing the performance of NCC-CuSpwith NCC-EDTA