“…Accordingly, much effort has gone into developing improved immunoassay methods for quantitative Abbreviations: hPI, human proinsulin; RIA, radioimmunoassay; ELISA, enzymelinked immunosorbant assay; HPLC, high performance liquid chromatography; SEC, size-exclusion chromatography; cpm, counts per min. ଝ This manuscript reviews and summarizes work that was conducted at the determination of circulating concentrations of total, intact peptide [3,[18][19][20] and cleaved metabolites [21,22]. Early RIA methodology tended to detect both intact peptide and cleaved metabolites [23][24][25], while more recent sandwich ELISAs and related immunoanalytical methodologies have permitted the specific detection of intact peptide [3,19,20,21] and cleaved metabolites [22,23,27].…”