The analytical specificity of human chorionic gonadotropin assays determined using WHO International Reference Reagents

Background: Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone with considerable molecular heterogeneity. There is uncertainty regarding which hCG variants are detected by different hCG assays. The analytical specificity of 8 hCG assays was investigated. Methods: WHO International Reference Reagents for hCG, nicked hCG (hCGn), beta subunit (hCG beta), nicked beta subunit (hCG beta n), and beta core fragment (hCG beta cf) were individually added to hCG-free human serum. Specimens were analyzed with 8 commercially available hCG assays. Equimolar detection of hCG variants was defined as a recovery. of 90-110%. Results: All assays detected hCG and hCGn with mean recoveries of 98.3 and 94.6%, respectively. Seven assays detected hCG beta (mean recovery 103.8%) but with high variation. and equimolar detection was observed only in four. The mean recovery of hCG beta n was 85.5% but was highly variable with only two assays showing equimolar detection. With a mean recovery of 53.4%, two assays detected hCG beta cf and both underestimated it considerably. Information provided by the assay manufacturer regarding hCG variant analytical specificity was inadequate or unclear in 75% of the assays. Conclusions: hCG assays vary considerably in their ability to detect different hCG variants. Manufacturers of hCG assays should clearly indicate the hCG variant specificity of their reagent systems. (C) 2009 Elsevier B.V. All rights reserved.