Standardization of Assays for Human Chorionic Gonadotropin

The unsatisfactory standardization of many immunoassays is fairly well recognized, but the problem is hard to tackle (1). Recently, studies on the performance of immunoassays for testosterone in female serum (2) and for urinary cortisol (1) have revealed that the quality of some widely used assays is totally unsatisfactory. The quality of assays for human chorionic gonadotropin (hCG) has also been shown to be problematic (3)(4), and this was a reason for the IFCC to establish a working group for standardization of assays for this hormone. In addition to being a clinically important analyte, hCG immunoreactivity in biological fluids comprises a reasonable number of well-known variants. hCG was thus considered a suitable model for standardization of glycoprotein hormones in general (5).It has been argued that it is impossible to standardize assays for heterogeneous antigens (6), and an important aim of the IFCC committee on hCG was to study whether this is the case. Other aims were to introduce a uniform nomenclature, to prepare new standards, and to assign values to these in substance concentrations (mol/L). Standards should preferably be pure, identical to the analyte in serum, and homogeneous, but glycoproteins are inherently heterogeneous because of variation in the carbohydrate moieties. Standards for subunits and degraded forms of hCG occurring in circulation were also needed (5). The working group of the IFCC has achieved most of its goals. Standards for hCG and its most important variants, i.e., its β- and α-subunits (hCGβ and hCGα), the core fragment of hCGβ (hCGβcf), and two partially cleaved or “nicked” forms (hCGn and hCGβn), are now available from WHO as the 1st Research Reagents (1st RRs) (7). The hCG preparation was used by Cole et al. (8) to study how nine widely used immunoassays for hCG are standardized. In addition, the …